European Organization Of Research And Treatment Of Cancer Research Articles

Application of electroacupuncture in the prevention of low anterior resection syndrome after rectal cancer surgery.

Low anterior resection syndrome (LARS) is one of the common postoperative complications in patients with rectal cancer, which seriously affects their postoperative recovery and quality of life (QoL). Electroacupuncture therapy is one of the characteristic therapies of traditional Chinese medicine. There are few reports on the prevention and treatment of LARS by electroacupuncture therapy. To explore the clinical effectiveness of electroacupuncture in managing rectal cancer patients with postoperative LARS. A total of 50 patients with LARS after rectal cancer surgery were retrospectively selected as the research subjects. According to the treatment methods, they were divided into an observation group (n = 25) and a control group (n = 25). During the four-week treatment period, the control group received standard defecation function training, while the observation group received electroacupuncture care and traditional defecation function training. The anal pressure index (which includes anal resting pressure, anal systolic pressure, and maximum tolerable volume), European Organization of Research and Treatment of Cancer (EORTC) QoL C30 (QLQ-C30) score, LARS Scale (LARSS) score, Wexner anal incontinence scale score, Xu Zhongfa five-item 10-point scale score, and the occurrence of adverse reactions were compared between the two groups before and after treatment. The experimental group showed considerably enhanced LARSS scores compared to those in the control group after four weeks of treatment. In the first week, second week, and fourth week, the LARSS score and Wexner anal incontinence scale score decreased, and the Xu Zhong method five-item 10-point scale score increased, with significant differences (P < 0.05). The experimental group showed substantial improvements in anal resting pressure, anal systolic pressure, and maximum tolerance volume after undergoing 4 wk of therapy in the untreated group (P < 0.05). The experimental group's QLQ-C30 score on the EORTC QoL questionnaire was higher than that of the control group during the 1st, 2nd, and 4th wk (P < 0.05). No significant variation between the groups in the frequency of adverse reactions (P > 0.05) was observed. Electroacupuncture positively impacted LARS following rectal cancer surgery, effectively improving clinical symptoms and anal pressure indicators and patients' standard of life.

European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention–Update 2023

Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in white populations, accounting for 20% of all cutaneous malignancies. Overall, cSCC mostly has very good prognosis after treatment, with 5-year cure rates greater than 90%. Despite the overall favourable prognosis and the proportionally rare deaths, cSCC is associated with a high total number of deaths due to its high incidence. A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS), the European Academy of Dermatology and Venereology (EADV) and the European Organization of Research and Treatment of Cancer (EORTC), was formed to update recommendations on cSCC, based on current literature and expert consensus. Part 1 of the guidelines addresses the updates on classification, epidemiology, diagnosis, risk stratification, staging and prevention in immunocompetent as well as immunosuppressed patients.

Association of MGMT Promoter Methylation With Survival in Low-grade and Anaplastic Gliomas After Alkylating Chemotherapy

O6-methylguanine-DNA methyltransferase (MGMT [OMIM 156569]) promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy for glioblastomas and is routinely used to guide treatment decisions. However, the utility of MGMT promoter status for low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large data sets. To evaluate the association of mMGMT for low-grade and anaplastic gliomas with chemotherapy response. This cohort study aggregated grade II and III primary glioma data from 3 prospective cohort studies with patient data collected from August 13, 1995, to August 3, 2022, comprising 411 patients: MSK-IMPACT, EORTC (European Organization of Research and Treatment of Cancer) 26951, and Columbia University. Statistical analysis was performed from April 2022 to January 2023. MGMT promoter methylation status. Multivariable Cox proportional hazards regression modeling was used to assess the association of mMGMT status with progression-free survival (PFS) and overall survival (OS) after adjusting for age, sex, molecular class, grade, chemotherapy, and radiotherapy. Subgroups were stratified by treatment status and World Health Organization 2016 molecular classification. A total of 411 patients (mean [SD] age, 44.1 [14.5] years; 283 men [58%]) met the inclusion criteria, 288 of whom received alkylating chemotherapy. MGMT promoter methylation was observed in 42% of isocitrate dehydrogenase (IDH)-wild-type gliomas (56 of 135), 53% of IDH-mutant and non-codeleted gliomas (79 of 149), and 74% of IDH-mutant and 1p/19q-codeleted gliomas (94 of 127). Among patients who received chemotherapy, mMGMT was associated with improved PFS (median, 68 months [95% CI, 54-132 months] vs 30 months [95% CI, 15-54 months]; log-rank P < .001; adjusted hazard ratio [aHR] for unmethylated MGMT, 1.95 [95% CI, 1.39-2.75]; P < .001) and OS (median, 137 months [95% CI, 104 months to not reached] vs 61 months [95% CI, 47-97 months]; log-rank P < .001; aHR, 1.65 [95% CI, 1.11-2.46]; P = .01). After adjusting for clinical factors, MGMT promoter status was associated with chemotherapy response in IDH-wild-type gliomas (aHR for PFS, 2.15 [95% CI, 1.26-3.66]; P = .005; aHR for OS, 1.69 [95% CI, 0.98-2.91]; P = .06) and IDH-mutant and codeleted gliomas (aHR for PFS, 2.99 [95% CI, 1.44-6.21]; P = .003; aHR for OS, 4.21 [95% CI, 1.25-14.2]; P = .02), but not IDH-mutant and non-codeleted gliomas (aHR for PFS, 1.19 [95% CI, 0.67-2.12]; P = .56; aHR for OS, 1.07 [95% CI, 0.54-2.12]; P = .85). Among patients who did not receive chemotherapy, mMGMT status was not associated with PFS or OS. This study suggests that mMGMT is associated with response to alkylating chemotherapy for low-grade and anaplastic gliomas and may be considered as a stratification factor in future clinical trials of patients with IDH-wild-type and IDH-mutant and codeleted tumors.

Sexual dysfunction is highly prevalent in male survivors of malignant lymphoma.

With improved survival in patients with lymphoma, long-term toxicity and quality of life (QoL), including sexual health, have become increasingly important. We aimed to (1) determine the prevalence of erectile dysfunction (ED) in adult male lymphoma survivors; (2) determine whether testosterone deficiency, comorbidities, or lifestyle factors were associated; and (3) evaluate their impact on QoL. A cross-sectional study including 172 male survivors of Hodgkin lymphoma or diffuse large B cell lymphoma diagnosed in adulthood between 2008 and 2018 was performed. Patients were in complete metabolic remission after first-line treatment and remained in remission at follow-up (3-13years after diagnosis). Participants completed 3 questionnaires measuring sexual health and general QoL. Serum concentrations of total testosterone were measured and thorough medical history and sociodemographic factors were obtained. The Danish SEXUS Project, European Male Ageing Study, and European Organization of Research and Treatment of Cancer (EORTC) Reference Manual were used as reference values of the general population. Patient reported outcome measures including the 5-item International Index of Erectile Function, EORTC C30, and EORTC 22-item Sexual Health Questionnaire. ED was reported by 55.2%, which was higher than in an age-matched Danish population cohort (17.5%). Erectile function score (5-item International Index of Erectile Function) was negatively associated with comorbidity, body mass index, smoking, and age and positively with the number of children conceived before treatment and serum concentration of total testosterone. Overt testosterone deficiency in combination with ED was detected in 10 (5.7%) of 176 survivors, including excluded survivors in hormonal treatment, which is higher than for the general population (0.1%-3.2% for men <70years of age). Mean EORTC C30 global health score for survivors with ED was lower (67.7) than for survivors without ED (80.1) but was comparable to the general population (71.2). Furthermore, a positive association was seen between sexual function and both sexual and general QoL. Sexual health is important for QoL and related to comorbidities. The focus on improving QoL requires that both sexual health and comorbidities are addressed in the follow-up of lymphoma patients. Despite the relatively high number of included survivors, the cross-sectional design of this study warrants longitudinal studies to clarify the specific underlying causes of sexual dysfunction. ED was highly prevalent and associated with comorbidity in lymphoma survivors, and more focus on sexual health and treatment related comorbidity is needed to improve sexual and general QoL.

Quality of life and Its Determinants among Cervical Cancer Patients in South India.

Cervical Cancer is the leading cause of morbidity and mortality in India. It affects the patient's, physical and psychological state which results in lower quality of life (QoL). Women with cervical cancer may require counselling and time to enable them to deal with the disease and its treatment. The present study aimed to determine the quality of life and its determinants among cervical cancer patients. A cross-sectional study was undertaken from April 2017 to September 2017 in a regional cancer centre in South India. Cervical cancer patients (N= 210) with histological confirmation were interviewed at the hospital. European Organization of Research and Treatment of Cancer (EORTC) questionnaire core module, QLQ-C30 Version 3.0, and recommended scoring algorithm were used to measure and analyse QoL. The Association of socio-economic determinants on quality of life was evaluated using multiple logistic regression. Among 210 cervical cancer patients enrolled, the majority 106 (50.5%) of women were between the age group 46 to 59 years and most, i.e. 167(63.0%) were not literate. The median score in the global health status was 50.0[IQR 33.3 - 66.7], 66.7[IQR 60.0 - 80.0] in physical functioning, and 83.3[IQR 66.7 - 83.3] in pain symptoms respectively which were poor compared to reference score of EORTC for all normal females and those with any cancer. The factors which were significantly associated with the GHS QoL score were the advanced stage of disease (OR:2.1, 95%CI: 1.1 - 3.9) and the age of the patients ≥60 years compared with ≤ 45 years (OR:18.4, 95%CI: 6.8 - 50.1). Cervical cancer patients had poor global health status compared to the reference score for all females with any cancer and the normal females. Advanced stage of cancer and older age have a significant association with QoL.

The patient-reported outcome measures in oropharyngeal, laryngeal and hypopharyngeal cancer patients treated with Volumetric Modulated Arc based simultaneous integrated boost radiotherapy.

To assess the change in the quality of life (QOL) in head and neck cancer patients treated with Simultaneous Integrated Boost (SIB) by Volumetric Modulated Arc Therapy (VMAT) technique. Thirty patients with localised head and neck cancers (Stage II- IVa) were treated with VMAT and SIB technique. The three-dose levels prescribed were 68.2 Gy at 2.2 Gy/fraction, 62 Gy at 2 Gy/fraction and 55.8 Gy at 1.8 Gy/fraction to the high, intermediate and low-risk volumes respectively. Concurrent chemotherapy with cisplatin 100 mg/m2 was administered once in three weeks. Acute toxicities were evaluated and scored according to the RTOG grading system. Quality of life (QOL) was assessed using European Organization of Research and Treatment of Cancer (EORTC) QLQC30 and HN35 questionnaires at baseline and in three instances (immediately, one month and three months after the radiotherapy). Out of the total 30, 80% patients had a complete response (CR) at the median follow up of 12 months, while three patients died because of progression, and the remaining 3 had stable disease. All planning objectives were achieved for organs at risk and planning target volume(PTV). There was a statiscally significant(p value < 0.001) reduction in global quality of life scores at the end of treatment when compared to baseline scores, but by three months, there was the return in the QOL scores in most scales similar to the baseline value. VMAT based Simultaneous boost radiotherapy is a feasible and safe strategy in terms of toxicityprofile with an acceptable transient change in the quality of life and allows a faster return to baseline quality of life.

Survival and Patient-Reported Outcomes of Older Adults with Primary Central Nervous System Lymphoma on Low-Dose Lenalidomide

Introduction: Management of primary CNS lymphoma (PCNSL) in patients age &amp;gt;70 represents a significant challenge. In most clinical series, median OS for PCNSL patients age &amp;gt;70 is &amp;lt;1 year (Mendez et al., Neuro-Oncology 2018). Since late 2011, our group has used low-dose lenalidomide as maintenance therapy in older patients with newly-diagnosed PCNSL who had &amp;gt;partial response (PR) to induction chemotherapy or salvage chemotherapy for relapsed disease. A preliminary report by our group supported the feasibility and efficacy of low-dose lenalidomide maintenance for 13 older patients with PCNSL, in lieu of consolidation with radiation or high-intensity chemotherapy (Vu et. al., BJH 2019).Here, we present the outcomes of 22 consecutive older patients with PCNSL (inclusive of updated outcomes on the original 13 patients) treated with low-dose lenalidomide after achieving &amp;gt;PR following induction chemotherapy. In addition, we provide a first report on the impact of maintenance low-dose lenalidomide on quality of life (QOL), overall functioning, and symptom burden. Methods: We performed a retrospective analysis of consecutive patients age &amp;gt;65 years with PCNSL, who achieved &amp;gt;PR to induction methotrexate/rituximab+temozolomide (MTR) chemotherapy and were subsequently treated with low-dose lenalidomide maintenance (5-10 mg/dose) in PR1/CR1. We determined their clinical characteristics, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier. In addition, we obtained correlative data on QOL and symptom burden on a representative sample of older PCNSL patients who were treated with low-dose IMiDs over the course of &amp;gt; 2 months, via the European Organization of Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ)-C30. Our study was approved by the University of California San Francisco Institutional Review Board with patient informed consent. Results: The median age at diagnosis of the 22 consecutive older newly-diagnosed PCNSL patients was 77 (range 64 - 86). Median Karnofsky Performance Status was 70. Twenty patients received induction MTR (2 received M-R) without consolidative dose-intensive chemotherapy, autologous stem cell transplant, or whole brain irradiation. The median methotrexate dose was 2.5 gm/m2 (range 0.5 - 8). With median follow-up of 47 months, median time on low-dose lenalidomide maintenance was 14 months. Median PFS was 84 months, and median OS has not been reached. (Figure 1). At progression, patients received methotrexate followed by lenalidomide or pomalidomide. Thus far, there have been 3 deaths: one due to PCNSL, one by myocardial infarction, 4 years after discontinuation of lenalidomide, and one without definitive cause. To assess the tolerability of low-dose lenalidomide (and/or pomalidomide) in this population, we determined patient-reported outcomes with respect to quality of life, as measured by the EORTC QLQ-C30. We summarize our findings in Figure 2 on 8 consecutive PCNSL patients age &amp;gt;70 that received maintenance IMiD therapy for at least 2 months. Seven of the 8 patients were treated with maintenance low-dose lenalidomide for a median of 11 months, and one patient was on maintenance pomalidomide (1-2 mg/day) for a total of 76 months. Overall low-dose IMiDs were well-tolerated: mild-to-moderate fatigue and insomnia were the two most commonly reported symptoms. Conclusions: Our experience suggests that low-dose lenalidomide as maintenance therapy after induction chemotherapy in older patients with PCNSL may result in improved PFS and OS. Importantly, our data suggest that QOL and overall functioning as measured by the EORTC QLQ-C30 was comparable, if not better, than QOL as assessed for patients receiving high dose methotrexate-based therapy, autologous stem cell transplant, whole brain radiation therapy, and/or blood brain barrier disruption (Doolittle et. al., Neurology 2013). In conclusion, based on this preliminary assessment, maintenance low-dose lenalidomide (and pomalidomide) appear to be well-tolerated in older PCNSL, with patients reporting good quality of life, low symptom burden, and overall good level of functioning. Survival outcomes remain encouraging. A phase I trial in newly-diagnosed, non-transplant eligible PCNSL that evaluates combination nivolumab with lenalidomide, both as a component of induction therapy and as low-dose lenalidomide maintenance, is in development via Alliance (A051901). Disclosures Rubenstein: Kymera: Research Funding. OffLabel Disclosure: Low-Dose Lenalidomide as Maintenance in Older Patients with Primary CNS Lymphoma

Determination of immunophenotypic aberrancies provides better assessment of peripheral blood involvement by mycosis fungoides/Sézary syndrome than quantification of CD26- or CD7- CD4+ T-cells.

Blood involvement by mycosis fungoides (MF)/Sézary syndrome (SS) influences prognosis and therapeutic decisions. MF/SS blood stage is currently determined by absolute CD4 + CD26- or CD4 + CD7-cell counts, which quantification method may overestimate MF/SS by including CD26- or CD7- normal CD4+ T-cells, or underestimate disease burden when MF/SS cells show incomplete loss of CD26 and/or CD7. Recently, through the standardization effort led by the International Clinical Cytometry Society (ICCS), recommendation was made to quantify MF/SS by enumerating immunophenotypically aberrant CD4+ T-cells, rather than CD26- or CD7- in isolation. We compared these two quantitation methods in 309 MF/SS patients who had blood samples analyzed by flow cytometry immunophenotyping (FCI) over a 1-year period. Using the European Organization of Research and Treatment of Cancer (EORTC)/International Society for Cutaneous Lymphomas (ISCL) criteria, 221 (71.5%) patients had a blood stage corresponding to B0, 57 (18.4%) to B1, and 31 (10%) to B2. By FCI analysis, a total of 62 patients (20.0%) were found positive for MF/SS. Among EORTC B0 patients, 11/221 (5%) were positive by FCI (false negatives), and among EORTC Stage B1 patients, 35/57 (61%) were negative by FCI (false positives). Regarding patients positive for MF/SS cells by FCI, there was an overall excellent correlation (r = .999, p < .001) between the EORTC/ISCL method and FCI method; however, four (6.5%) patients would have an altered B stage between B0 and B1. The MF/SS cell quantification method using immunophenotypic aberrancies, as recommended by the ICCS, allows to distinguish MF/SS cells from background benign T-cells and enables for more accurate staging, especially among patients currently being considered to have B0 and B1 stage diseases.

Red cell distribution width predicts time to recurrence in patients with primary non–muscle-invasive bladder cancer and improves the accuracy of the EORTC scoring system

PurposeTo investigate the clinical prognostic value of red cell distribution width (RDW) in patients with non–muscle-invasive bladder cancer (NMIBC). Materials and methodsWe retrospectively evaluated 582 consecutive patients with primary NMIBC. The efficacy of preoperative RDW at predicting treatment outcome was assessed. A cut-off point for predicting recurrence was also identified. Uni- and multivariable analyses of time to recurrence (TTR) and progression were conducted. Harrell's concordance index (c-index) was used to evaluate the additive value of RDW to the European Organization of Research and Treatment of Cancer (EORTC) risk scoring model for recurrence. ResultsAccording to the receiver operating characteristic curve of RDW for recurrence, a RDW ≥ 14.5% was classified as high. In the multivariable analysis, a high RDW could independently predict shorter TTR (subdistribution hazard ratio [SHR]: 2.65, 95% confidence interval [CI]: 1.83–3.84, P < 0.001), irrespective of tumor characteristics. No significant relationship was observed between RDW and time to progression (SHR: 1.75, 95% CI: 0.76–4.08, P = 0.19). Adding binary-coded RDW to the EORTC risk scoring model significantly improved its discriminatory performance in assessing recurrence risk (c-index: 0.62, improvement: 0.052, P < 0.001). High RDW was associated with shorter TTR in patients treated with bacillus Calmette-Guerin in the multivariable analysis (SHR: 2.0, 95% CI: 1.01–3.98, P = 0.047). ConclusionsRDW was an independent, significant prognostic factor of TTR in patients with primary NMIBC. Adding RDW to the EORTC risk model significantly improved the model's predictability for tumor recurrence.

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics – Update 2019

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed through dermatoscopy. If a melanoma is suspected, a histopathological examination is required. Sequential digital dermatoscopy and full-body photography can be used in risk persons to detect the development of melanomas at an earlier stage. Where available, confocal reflectance microscopy can improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the AJCC classification. Thin melanomas up to 0.8 mm tumor thickness does not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC whole-body examinations with CT or PET-CT in combination with brain MRI are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to support the frequency and extent of examinations. A stage-based follow-up scheme is proposed, which, according to the experience of the guideline group, covers the minimum requirements; further studies may be considered. This guideline is valid until the end of 2021.

The role of neutrophil to lymphocyte ratio in patients with pTa non-muscle invasive bladder cancer

Abstract Introduction: The peritumoral inflammatory reaction has a substantial importance in the oncologic outcome of bladder cancer (BC). One biomarker proven to be practical and accessible is the NLR (neutrophil-to-lymphocyte ratio) for high risk non-muscle invasive bladder cancer (NMIBC). The aim of the study was to investigate the role of NLR as a prognostic biomarker for disease recurrence, progression and survival of p Ta (pathological assesment of the primary tumor) NMIBC. Material and Methods: In our retrospective study we included 54 patients with pTa NMIBC from a total of 235 patients who underwent transurethral resection of bladder tumor (TURBT) during two consecutive years: January 2007 - December 2008 [median follow-up 106 months (interquartile range-IQR 68-116)]. Criteria for inclusion were: primary tumor, low-grade, with NLR available at 2 weeks prior to TURBT. NLR was considered altered if higher than 3. Results: The median age of the patients included was 63 years (IQR 55 - 72). Most of the patients had NLR---lt---3 (37 patients). Median EORTC (European Organization of Research and Treatment of Cancer) Recurrence Score was 4 (IQR 1-6), while EORTC Progression Score was 3 (IQR 0-6), respectively. Recurrence occurred in 8 out of 54 (14.81 %) patients and progression was identified in 2 out of 54 (3.70 %) patients with muscle-invasive BC during follow-up. NLR---gt---3 was not associated with clinical and pathological factors. In multivariable Cox regression analyses NLR as a continuous variable was an independent predictive factor for recurrence. Recurrence-free survival (RFS) Kaplan-Meier analysis did not show a statistical significance between NLR groups: 82.67% vs. 64.12%, p=0.26. Kaplan-Meier analysis showed a lower Progression-free survival (PFS) in the NLR---gt---3 group: 94.12% vs. 100%, p=0.04. During follow-up (106 months) 18 patients deceased with no impact of NLR as a prognostic factor in multivariable analyses. Kaplan-Meier overall survival (OS) analysis showed a 10-year OS of 70.27% in the low NLR group compared with 58.82% in the high NLR group, p=0.45. Conclusion: In this cohort, high NLR was associated with high recurrence rate in patients with Ta NMIBC. In low-risk NMIBC NLR could represent a valid biomarker for clinical usage regarding the intensity of follow-up schedule.

Hypoalbuminemia as a relapse risk factor after high dose chemotherapy and autologous stem cell transplantation in patients with Hodgkin’s lymphoma

Assessing the risk factors according to EORTC (European Organization of Research and Treatment of Cancer) or HD IPS (Hodgkin’s lymphoma International Prognostic Score) is crucial for choosing the adequate I line therapy in Hodgkin’s lymphoma patients. However, none of those scales predicts the efficacy of autologous stem cell transplant (ASCT) in relapsing/refractory (R/R) patients. Progression- free survival (PFS) after ASCT corelates with the response to salvage regimens. Thirty-nine Hodgkin’s lymphoma patients transplanted at Jagiellonian University Department of Hematology with a follow-up exceeding 5 years were analyzed. Despite long time periods since the diagnosis, initial serum albumin levels seem to correlate with progression after autologous stem cell transplant and indicate high probability of relapse within 5 months following the procedure with favorable test characteristics.

Опросник качества жизни для пациентов с онкоортопедической патологией

European Organization of Research and Treatment of Cancer (EORTC) Bone Metastases (BM22), developed by the Quality of Life Assessment Group, is a specialized module of the quality of life questionnaire EORTC QLQ-C30, assessing the quality of life in patients with bone tumors. The aim of the study is to develop its Russian version. The study included a sample of 139 patients with bone tumors — inpatients of N.N. Blokhin Cancer Research Center. The scale has a good convergent validity and internal consistency (0,871), factor analysis confirmed the structure of the scale and its compliance with the original model. The results revealed significant decrease in quality of life due to patients’ focus on pain and its severity. We conclude by drawing out the main directions of psychological aid to patients with bone tumors.

Effect of Hypofractionated, Palliative Radiotherapy on Quality of Life in Late-Stage Oral Cavity Cancer: A Prospective Clinical Trial.

Context:The study was designed to evaluate the effect of a hypofractionated, palliative conformal radiotherapy regimen of 5250 cGy in 15 fractions in inoperable/incurable oral cavity carcinoma.Aims:The primary objective was to assess the change in the quality of life (QOL) with respect to pain and mouth opening pre- and post-radiotherapy using standardized questionnaires. The secondary objective was to assess overall QOL using the same questionnaires and also to assess response rates, survival, compliance, early and late toxicity.Settings and Design:This was a single-arm, prospective trial. Patients with incurable oral cavity cancer referred for palliative intent radiotherapy to the Department of Radiotherapy, RCC, JIPMER were recruited into the study.Subjects and Methods:Forty-eight patients were recruited and twenty-five patients were given conformal radiotherapy to a dose of 52.5 Gy in 15 fractions. QOL was assessed using the European Organization of Research and Treatment of Cancer (EORTC) questionnaires before and 2 months after the completion of radiotherapy. The response assessment was made using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 2 months after radiotherapy. The early and late toxicities were assessed at 2 months and 6 months after radiotherapy completion, respectively.Statistical Analysis Used:Sample size was calculated to be 53. The Wilcoxon signed-rank test was used to compare QOL scores pre- and post-radiotherapy. Median survival was assessed using the Kaplan–Meier method.Results:There was a significant improvement in the pain, mouth opening, speech, social contact, social eating, felt ill items of the EORTC QLQ-H and N35 questionnaire and role functioning, emotional functioning, social functioning, fatigue, pain, insomnia, appetite loss, financial difficulties, and Global QOL subscales of the QLQ-C30 questionnaire. 72% of the patients had grade 3 acute radiation oral mucositis and 36% had grade 3 acute radiation dermatitis. There were no significant treatment breaks due to toxicity. There were no grade 3 late toxicities observed. Overall median survival was 5.1 months. The overall response rate was 47%. The median time to treatment completion was 24 days.Conclusions:The improvement in QOL parameters suggests that the regimen of 52.5 Gy in 15 fractions is suitable for palliative intent radiotherapy in late-stage oral cavity cancer for effective palliation for short periods.

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary cutaneous lymphomas (PCLs) are defined as non-Hodgkin lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. After gastrointestinal lymphomas, PCLs are the second most common group of extranodal non-Hodgkin lymphomas, with an estimated annual incidence of 1/100 000 in Western countries. PCLs must be distinguished from nodal or systemic malignant lymphomas involving the skin secondarily, which often have another clinical behaviour, have a different prognosis and require a different therapeutic approach. In recent lymphoma classifications, PCLs are therefore included as separate entities. Within the group of PCLs, distinct types of cutaneous T cell lymphoma (CTCL) and cutaneous B cell lymphoma (CBCL) can be distinguished [1.Willemze R. Jaffe E.S. Burg G. et al.WHO–EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768-3785Crossref PubMed Scopus (3224) Google Scholar, 2.WHO Classification of Tumours Haematopoietic and Lymphoid Tissues.in: Swerdlow S.H. Campo E. Harris N.L. 4. IARC, Lyon2017Google Scholar]. In the Western world, CTCLs constitute ∼75%–80% of all PCLs [with mycosis fungoides (MF) as the most common type of CTCL] and CBCL ∼20%–25% [1.Willemze R. Jaffe E.S. Burg G. et al.WHO–EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768-3785Crossref PubMed Scopus (3224) Google Scholar]. However, different distributions have been observed in other parts of the world. In Southeast Asian countries, CTCLs other than MF [in particular Epstein–Barr virus-associated natural killer (NK)/T cell lymphomas] are much more common than in Western countries, while CBCLs are much more uncommon [3.Tan S.H. Sim C.S. Ong B.H. Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems.Br J Dermatol. 2003; 149: 542-553Crossref PubMed Scopus (30) Google Scholar, 4.Park J.H. Shin H.T. Lee D.Y. et al.World Health Organization–European Organization for research and treatment of cancer classification of cutaneous lymphoma in Korea: a retrospective study at a single tertiary institution.J Am Acad Dermatol. 2012; 67: 1200-1209Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar]. PCLs are rare diseases and patients should ideally be seen by a multidisciplinary team of dermatologists, pathologists, haematologists and radiation oncologists. The diagnosis and classification of PCLs should always be based on a combination of clinical, histological, immunophenotypical and genetic data. Demonstration of clonal T cell receptor or immunoglobulin gene rearrangements in lesional skin or peripheral blood may be a valuable adjunct in selected cases. However, clinical and histopathological features are, in most cases, the most important deciding factors for therapeutic planning. PCLs should be classified according to the criteria of the revised 2017 World Health Organization (WHO) classification ( see Table 1) [2.WHO Classification of Tumours Haematopoietic and Lymphoid Tissues.in: Swerdlow S.H. Campo E. Harris N.L. 4. IARC, Lyon2017Google Scholar].Table 1WHO-EORTC classification for cutaneous lymphomasCutaneous T cell lymphomaMycosis fungoides (MF)Variants of MF•Folliculotropic MF•Pagetoid reticulosis•Granulomatous slack skinSézary syndromePrimary cutaneous CD30+ lymphoproliferative disorders•Primary cutaneous anaplastic large cell lymphoma•Lymphomatoid papulosisSubcutaneous panniculitis-like T cell lymphomaExtranodal NK/T cell lymphoma, nasal-typePrimary cutaneous peripheral T cell lymphoma-not otherwise specified•Primary cutaneous γ/δ T cell lymphoma•Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphomaaProvisional entities.•Primary cutaneous acral CD8+ T cell lymphomabNew provisional entity in the revised 2017 WHO classification [2].•Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorderaProvisional entities.Cutaneous B cell lymphomaPrimary cutaneous marginal zone lymphomaPrimary cutaneous follicle centre lymphomaPrimary cutaneous diffuse large B cell lymphoma, leg typeEORTC, European Organization of Research and Treatment of Cancer; NK, natural killer; WHO, World Health Organization.Adapted from [1.Willemze R. Jaffe E.S. Burg G. et al.WHO–EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768-3785Crossref PubMed Scopus (3224) Google Scholar] with permission.a Provisional entities.b New provisional entity in the revised 2017 WHO classification [2.WHO Classification of Tumours Haematopoietic and Lymphoid Tissues.in: Swerdlow S.H. Campo E. Harris N.L. 4. IARC, Lyon2017Google Scholar]. Open table in a new tab EORTC, European Organization of Research and Treatment of Cancer; NK, natural killer; WHO, World Health Organization. Adapted from [1.Willemze R. Jaffe E.S. Burg G. et al.WHO–EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768-3785Crossref PubMed Scopus (3224) Google Scholar] with permission. In all cases, adequate staging should be carried out to exclude the presence of extracutaneous disease. Recommendations for the initial staging of patients with MF/Sézary syndrome (SS) are presented in Table 2. Flow cytometry of the peripheral blood is usually recommended for all stages of MF. However, it is debatable whether this test is justified in patients who are not suspected to have SS. Computed tomography (CT) and/or fluorodeoxyglucose-positron emission tomography (FDG-PET) scans are optional in early-stage MF. Bone marrow examination is usually not indicated in patients with MF/SS.Table 2Recommendations for staging evaluation in patients with MF/SS [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar]Complete physical examination including:•Determination of type(s) of skin lesions•Identification of any palpable lymph node, especially those ≥ 1.5 cm in largest diameter or firm, irregular, clustered or fixed•Identification of any organomegalySkin biopsy•Most indurated area if only one biopsy•Routine histology and immunophenotyping•Evaluation for clonality of TCR gene rearrangement (optional)Blood tests•CBC with manual differential, liver function tests, LDH, comprehensive chemistries•TCR gene rearrangement and relatedness to any clone in skin (optional)•Analysis for abnormal lymphocytes by either Sézary cell count with determination absolute number of Sézary cells and/or flow cytometry (including CD4+/CD7– or CD4+/CD26–) (optional)Radiological tests•CT scans of chest, abdomen and pelvis alone ± FDG-PET (optional in patients with early-stage MF)Lymph node biopsy•Excisional biopsy in patients with a node that is either ≥ 1.5 cm in diameter and/or is firm, irregular, clustered or fixed•Routine histology, immunohistochemistry and TCR gene rearrangement analysisCBC, complete blood count; CT, computed tomography; FDG-PET, fluorodeoxyglucose-positron emission tomography; LDH, lactate dehydrogenase; MF, mycosis fungoides; SS, Sézary syndrome; TCR, T cell receptorAdapted from [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar] with permission from the American Society of Hematology; permission conveyed through Copyright Clearance Center, Inc. Open table in a new tab CBC, complete blood count; CT, computed tomography; FDG-PET, fluorodeoxyglucose-positron emission tomography; LDH, lactate dehydrogenase; MF, mycosis fungoides; SS, Sézary syndrome; TCR, T cell receptor Adapted from [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar] with permission from the American Society of Hematology; permission conveyed through Copyright Clearance Center, Inc. Initial work-up for patients with a PCL other than MF/SS also includes complete physical examination, representative skin biopsy, complete and differential blood cell count, routine serum biochemistry with lactate dehydrogenase (LDH) and appropriate imaging studies (CT and/or FDG-PET scans) [5.Kim Y.H. Willemze R. Pimpinelli N. et al.TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 479-484Crossref PubMed Scopus (354) Google Scholar]. In PCLs with a predominantly subcutaneous presentation, such as subcutaneous panniculitis-like T cell lymphoma (SPTCL) and primary cutaneous gamma/delta T cell lymphoma (PCGD-TCL), FDG-PET is essential to evaluate the extent of disease. In patients with typical lymphomatoid papulosis (LyP) or primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder (LPD), CT and FDG-PET scans are not required. Bone marrow biopsy and aspirate should be carried out in cutaneous lymphomas with an intermediate or aggressive clinical behaviour but is not required in cutaneous lymphomas with an indolent clinical behaviour, unless indicated by other staging assessments [5.Kim Y.H. Willemze R. Pimpinelli N. et al.TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 479-484Crossref PubMed Scopus (354) Google Scholar, 6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar]. Bone marrow examination is not indicated in patients with primary cutaneous marginal zone lymphoma (PCMZL), but its significance in primary cutaneous follicle centre lymphomas (PCFCLs) is controversial [5.Kim Y.H. Willemze R. Pimpinelli N. et al.TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 479-484Crossref PubMed Scopus (354) Google Scholar, 7.Senff N.J. Kluin-Nelemans H.C. Willemze R. Results of bone marrow examination in 275 patients with histological features that suggest an indolent type of cutaneous B-cell lymphoma.Br J Haematol. 2008; 142: 52-56Crossref PubMed Scopus (53) Google Scholar]. Prognosis is extremely variable depending on the type of PCLs and the stage of disease. For clinical staging of MF and SS, the revised tumour, node, metastasis and blood (TNMB) staging system should be used (Tables 3 and 4) [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar]. Apart from clinical stage, older age, large cell transformation and increased LDH values have been identified as independent unfavourable prognostic factors in MF [8.Agar N.S. Wedgeworth E. Crichton S. et al.Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal.J Clin Oncol. 2010; 28: 4730-4739Crossref PubMed Scopus (569) Google Scholar, 9.Scarisbrick J.J. Prince H.M. Vermeer M.H. et al.Cutaneous Lymphoma International Consortium study of outcome in advanced stages of mycosis fungoides and Sézary syndrome: effect of specific prognostic markers on survival and development of a prognostic model.J Clin Oncol. 2015; 33: 3766-3773Crossref PubMed Scopus (266) Google Scholar, 10.Alberti-Violetti S. Talpur R. Schlichte M. et al.Advanced-stage mycosis fungoides and Sézary syndrome: survival and response to treatment.Clin Lymphoma Myeloma Leuk. 2015; 15: e105-e112Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar]. For PCLs other than MF/SS, a separate TNM classification system has been published [5.Kim Y.H. Willemze R. Pimpinelli N. et al.TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 479-484Crossref PubMed Scopus (354) Google Scholar]. This staging system is primarily meant to document extent of disease and cannot be used as a prognostic guide.Table 3Revised TNMB classification of MF/SS [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar]T (skin)T1Limited patch/plaque (involving < 10% of total skin surface)T2Generalised patch/plaque (involving ≥ 10% of total skin surface)T3Tumour(s)T4ErythrodermaN (lymph node)N0No clinically abnormal peripheral lymph nodesN1Clinically abnormal peripheral lymph nodes; histologically uninvolvedN2Clinically abnormal peripheral lymph nodes; histologically involved (nodal architecture uneffaced)N3Clinically abnormal peripheral lymph nodes; histologically involved [nodal architecture (partially) effaced]NxClinically abnormal peripheral lymph nodes; no histological confirmationM (viscera)M0No visceral involvementM1Visceral involvementB (blood)B0No circulating atypical (Sézary) cells (or < 5% of lymphocytes)B1Low blood tumour burden (≥ 5% of lymphocytes are Sézary cells, but not B2)B2High blood tumour burden (≥ 1000/µl Sézary cells and positive clone)MF, mycosis fungoides; SS, Sézary syndrome; TNMB, tumour, node, metastasis, blood.Reprinted from [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar] with permission from the American Society of Hematology; permission conveyed through Copyright Clearance Center, Inc. Open table in a new tab Table 4Revised clinical staging system for MF/SS [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar]Clinical stageIAT1N0M0B0-1IBT2N0M0B0-1IIAT1–2N1-2M0B0-1IIBT3N0–2M0B0-1IIIT4N0–2M0B0-1IVA1T1–4N0-2M0B2IVA2T1–4N3M0B0-2IVBT1–4N0–3M1B0-2MF, mycosis fungoides; SS, Sézary syndrome. Reprinted from [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar] with permission from the American Society of Hematology; permission conveyed through Copyright Clearance Center, Inc. Open table in a new tab MF, mycosis fungoides; SS, Sézary syndrome; TNMB, tumour, node, metastasis, blood. Reprinted from [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar] with permission from the American Society of Hematology; permission conveyed through Copyright Clearance Center, Inc. MF, mycosis fungoides; SS, Sézary syndrome. Reprinted from [6.Olsen E. Vonderheid E. Pimpinelli N. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar] with permission from the American Society of Hematology; permission conveyed through Copyright Clearance Center, Inc. The choice of treatment depends on the type of PCL and the stage of disease. Due to their heterogeneity and rarity, controlled clinical trials in PCLs are almost non-existent, with a few exceptions mainly concerning recently marketed drugs. Recommendations are therefore largely based on (retrospective) cohort studies and expert opinions discussed during consensus meetings of the European Organization of Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Group, the International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous Lymphoma Consortium (USCLC) and the International Lymphoma Radiation Oncology Group (ILROG), including consensus recommendations for clinical end points and response criteria in MF/SS [11.Olsen E.A. Whittaker S. Kim Y.H. et al.Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer.J Clin Oncol. 2011; 29: 2598-2607Crossref PubMed Scopus (457) Google Scholar]. Since early aggressive chemotherapy (ChT) is associated with considerable side effects but does not improve survival, a stage-adapted conservative therapeutic approach is recommended for MF and its variants [12.Kaye F.J. Bunn Jr, P.A. Steinberg S.M. et al.A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides.N Engl J Med. 1989; 321: 1784-1790Crossref PubMed Scopus (427) Google Scholar, 13.Trautinger F. Eder J. Assaf C. et al.European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome – update 2017.Eur J Cancer. 2017; 77: 57-74Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 14.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology; Mycosis fungoides/Sézary syndrome (Version 2.2018 – January 2, 2018). https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf (8 January 2017, date last accessed).Google Scholar, 15.Whittaker S. Hoppe R. Prince H.M. How I treat mycosis fungoides and Sézary syndrome.Blood. 2016; 127: 3142-3153Crossref PubMed Scopus (88) Google Scholar]. Patients with only patches and/or plaques covering < 10% (stage IA) or ≥ 10% of the skin surface (stage IB) should be treated with skin-directed therapies, including topical steroids, psoralens plus ultraviolet A (PUVA), narrow-band ultraviolet B (nb-UVB) and topical cytostatic agents, such as mechlorethamine (nitrogen mustard) (Figure 1). nb-UVB is recommended for patients with patches or very thin plaques but PUVA is preferred for patients with thicker plaques [III, A] [13.Trautinger F. Eder J. Assaf C. et al.European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome – update 2017.Eur J Cancer. 2017; 77: 57-74Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 15.Whittaker S. Hoppe R. Prince H.M. How I treat mycosis fungoides and Sézary syndrome.Blood. 2016; 127: 3142-3153Crossref PubMed Scopus (88) Google Scholar]. Topical steroids can be recommended as monotherapy for stage IA disease with patches/flat plaques. In stage IB, topical steroids can be used as adjuvant therapy for selected skin lesions. Topical application of mechlorethamine, either in aqueous solution or in an ointment-based preparation, has been used successfully for decades in the treatment of early-stage MF. A commercial 0.02% gel preparation was approved by the European Medicines Agency (EMA) as an orphan drug for the treatment of early stage MF [II, B] [16.Lessin S.R. Duvic M. Guitart J. et al.Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides.JAMA Dermatol. 2013; 149: 25-32Crossref PubMed Scopus (122) Google Scholar]. In patients developing one or few infiltrated plaques or tumours (stage IIB), additional low-dose local radiotherapy (RT) may suffice [III, A] [17.Neelis K.J. Schimmel E.C. Vermeer M.H. et al.Low-dose palliative radiotherapy for cutaneous B- and T-cell lymphomas.Int J Radiat Oncol Biol Phys. 2009; 74: 154-158Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar]. Local RT can be curative in patients with early localised disease, particularly in patients with unilesional MF and pagetoid reticulosis [IV, A]. In such patients, local RT is most commonly administered with electrons (energy dependent on the thickness of the lesion), with bolus to achieve full skin dose, a margin of ≥ 2 cm and a total dose of 20–24 Gy [IV, A] [18.Specht L. Dabaja B. Illidge T. et al.Modern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group.Int J Radiat Oncol Biol Phys. 2015; 92: 32-39Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar]. For patients with more extensive infiltrated plaques and tumours, or patients refractory to skin-directed therapies, systemic therapy with interferon alpha (IFNα) or retinoids (including bexarotene), commonly combined with PUVA or other skin-directed therapies, or a combination of IFNα and retinoids or total skin electron beam therapy (TSEBT), can be considered [III, B] [13.Trautinger F. Eder J. Assaf C. et al.European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome – update 2017.Eur J Cancer. 2017; 77: 57-74Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 15.Whittaker S. Hoppe R. Prince H.M. How I treat mycosis fungoides and Sézary syndrome.Blood. 2016; 127: 3142-3153Crossref PubMed Scopus (88) Google Scholar, 19.Quaglino P. Maule M. Prince H.M. et al.Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.Ann Oncol. 2017; 28: 2517-2525Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar]. TSEBT was often given to total doses of 30–36 Gy, but lower doses (10–12 Gy) have been employed with the advantages of shorter duration of the treatment period, fewer side effects and opportunity for re-treatment [III, A] [20.Hoppe R.T. Harrison C. Tavallaee M. et al.Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: results of a pooled analysis from 3 phase-II clinical trials.J Am Acad Dermatol. 2015; 72: 286-292Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 21.Kamstrup M.R. Gniadecki R. Iversen L. et al.Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis.Int J Radiat Oncol Biol Phys. 2015; 92: 138-143Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar]. In patients with advanced and refractory disease, gemcitabine or liposomal doxorubicin may be considered, but responses are generally short-lived [II, B] [22.Marchi E. Alinari L. Tani M. et al.Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients.Cancer. 2005; 104: 2437-2441Crossref PubMed Scopus (153) Google Scholar, 23.Dummer R. Quaglino P. Becker J.C. et al.Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012.J Clin Oncol. 2012; 30: 4091-4097Crossref PubMed Scopus (79) Google Scholar]. Other agents like the fusion toxin denileukin diftitox and histone deacetylase (HDAC) inhibitors, such as vorinostat and romidepsin, have been approved in the United States by the Food and Drug Administration (FDA) for patients with relapsed and refractory CTCL, but have not yet been registered for CTCL in Europe [24.Prince H.M. Duvic M. Martin A. et al.Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma.J Clin Oncol. 2010; 28: 1870-1877Crossref PubMed Scopus (184) Google Scholar, 25.Olsen E.A. Kim Y.H. Kuzel T.M. et al.Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.J Clin Oncol. 2007; 25: 3109-3115Crossref PubMed Scopus (877) Google Scholar, 26.Whittaker S.J. Demierre M.F. Kim E.J. et al.Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma.J Clin Oncol. 2010; 28: 4485-4491Crossref PubMed Scopus (543) Google Scholar]. Multi-agent ChT is only indicated in patients with effaced lymph nodes or visceral involvement (stage IV), or in patients with widespread tumour stage MF, which cannot be controlled with skin-targeted and immunomodulating therapies or who failed single-agent ChT, but—similar to single-agent ChT—responses are generally short-lived [IV, B] [27.Hughes C.F.M. Khot A. McCormack C. et al.Lack of durable disease control with chemotherapy for mycosis fungoides and Sezary syndrome: a comparative study of systemic therapy.Blood. 2015; 125: 71-81Crossref PubMed Scopus (150) Google Scholar]. Local palliation of cutaneous as well as extracutaneous lesions may be achieved with local RT to doses ≥ 8 Gy [III, A] [17.Neelis K.J. Schimmel E.C. Vermeer M.H. et al.Low-dose palliative radiotherapy for cutaneous B- and T-cell lymphomas.Int J Radiat Oncol Biol Phys. 2009; 74: 154-158Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar]. Recent studies report high response rates of brentuximab vedotin (BV; an anti-CD30 monoclonal antibody coupled to the anti-tubulin agent monomethyl auristatin E) in patients with advanced MF/SS expressing CD30 [II, B] [28.Duvic M. Tetzlaff M.T. Gangar P. et al.Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis.J Clin Oncol. 2015; 33: 3759-3765Crossref PubMed Scopus (220) Google Scholar, 29.Kim Y.H. Tavallaee M. Sundram U. et al.Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and Sézary syndrome with variable CD30 expression level: a multi-institution collaborative project.J Clin Oncol. 2015; 33: 3750-3758Crossref PubMed Scopus (208) Google Scholar, 30.Prince H.M. Kim Y.H. Horwitz S.M. et al.Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.Lancet. 2017; 390: 555-566Abstract Full Text Full Text PDF PubMed Scopus (358) Google Scholar]. In a phase II trial including 28 patients with CD30+ relapsed or refractory MF, BV showed a 54% overall response rate (ORR) with a median time to response of 12 weeks and a median duration of response of 32 weeks in patients with MF, independent of the degree of CD30 expression [28.Duvic M. Tetzlaff M.T. Gangar P. et al.Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis.J Clin Oncol. 2015; 33: 3759-3765Crossref PubMed Scopus (220) Google Scholar]. Another phase II study reported an ORR of 70% in a group of 32 patients with relapsed or refractory MF/SS with a wide range of CD30 expression levels [29.Kim Y.H. Tavallaee M

Health Related Quality of Life Results from the Open-Label, Randomized, Phase III Endeavor Trial Evaluating Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Introduction: The randomized, phase 3 study ENDEAVOR (NCT01568866; N=929) demonstrated a clinically meaningful and statistically significant improvement in progression-free survival for patients with relapsed or refractory multiple myeloma who were treated with carfilzomib and dexamethasone (Kd) versus bortezomib and dexamethasone (Vd; median, 18.7 vs 9.4 months; hazard ratio: 0.53; 95% confidence interval [CI]: 0.44-0.65; P<0.0001) (Dimopoulos et al. Lancet Oncol. 2016;17:27−38). Patient-reported outcomes (PROs) were included as exploratory endpoints in the ENDEAVOR study. Here, we present results of a prespecified analysis of health-related quality of life (HR-QoL) in the ENDEAVOR trial.Methods: HR-QoL was assessed by 3 validated instruments: the European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30-item questionnaire (QLQ-C30), the EORTC Quality of Life Questionnaire-multiple myeloma specific 20-item module (QLQ-MY20), and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) "Additional Concerns" neurotoxicity subscale. These instruments were assessed prior to treatment administration on day 1 of cycle 1, and then every 28 days until disease progression, withdrawal of consent, or commencement of other nonstudy anticancer treatment. Due to differing treatment cycle lengths, the PRO assessments coincided across groups every 12 weeks. The primary PRO hypothesis was superiority of Kd over Vd for the Global Health Status/Quality of Life (GHS/QoL) scale of the QLQ-C30. Seven further subscales were prespecified from the QLQ-C30 (fatigue, nausea/vomiting, pain, physical functioning, role functioning) and the QLQ-MY20 (disease symptoms, side effects of treatment).PRO subscales were compared between groups using a restricted maximum likelihood-based mixed model for repeated measures (MMRM). Two sensitivity analyses were performed for the GHS/QoL scale to evaluate the robustness of the MMRM to missing data. Clinical interpretation for the EORTC QLQ-C30 subscales was guided by pre-specifying minimum important differences (MIDs) based on evidence-based guidelines (5 points for the GHS/QoL scale). For the QLQ-MY20 subscales, the standard error of measurement was used as a proxy for the MID. The proportion of patients who had improved (≥5 points) from baseline on the GHS scale was summarized at each coinciding time point.Results: Baseline completion of the QLQ-C30 questionnaire was similar between groups (Kd, 87.7%; Vd, 84.3%). Compliance was high when calculated for all patients expected to provide a questionnaire at each time point (ie, alive and on-study), ranging from 73.1% to 93.9%. Median duration on study treatment was 40 weeks and 27 weeks for Kd and Vd patients, respectively. Using the MMRM model, Kd was associated with statistically significantly higher GHS/QoL scores compared with Vd (p<0.0001). However, the overall treatment difference point estimate of 3.5 (95% CI, 2.0-5.1) did not reach the pre-defined MID. When including the treatment by time interaction (p=0.28) to estimate the treatment difference at timepoints where HR-QoL assessments coincided with day 1 of a cycle, the point estimates increased over time, with the differences at week 60 and 72 reaching clinical significance (5.4 and 5.8, respectively) (Figure). Results from the two sensitivity analyses confirmed findings from the MMRM analysis. Statistically significant benefits were observed in favor of the Kd group for fatigue (P=0.04), pain (P=0.02), side effects (P<0.0001) and NTx subscales (p=0.0002), although these differences did not meet MID thresholds. The proportion of patients reaching a ≥5 point improvement in the GHS scale was numerically higher in the Kd group up to week 48, although the difference between the groups did not reach statistical significance.Conclusions: This analysis of PROs in the ENDEAVOR study demonstrated that Kd was statistically superior to Vd on the QLQ-C30 GHS/QoL scale, with clinically meaningful differences observed at later timepoints but not on average overall. For patients remaining on longer term treatment, the clinical benefits of Kd compared with Vd were associated with better GHS/QOL. Although not meeting MID thresholds, statistically significant benefits were also observed in favor of the Kd group for other aspects of HR-QoL. [Display omitted] DisclosuresLudwig:Janssen: Speakers Bureau; BMS: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau. Moreau:Amgen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria. Dimopoulos:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Glicomimetics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kaiser:BMS: Consultancy, Other: Travel Support; Takeda: Consultancy, Other: Travel Support; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy. Feng:Amgen: Employment, Equity Ownership. Cocks:Amgen: Consultancy; Celgene: Consultancy; BMS: Consultancy; Endomag: Consultancy. Buchanan:Amgen: Employment, Equity Ownership. Weisel:BMS: Consultancy, Honoraria; Novartis: Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Onyx: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

SALT II: A new take on the Severity of Alopecia Tool (SALT) for determining percentage scalp hair loss

To the Editor: The percentage scalp surface area (SSA) involved in various hair loss disorders is of interest for a variety of reasons including potential staging of a given condition, prognostic implications for hair regrowth, amount of drug application necessary for treatment, and efficacy assessments. We previously published a tool for determining degree of hair loss based on the percentage of SSA involved on the top, back, and each side of the scalp (Fig 1) that is used in the assessment of the Severity of Alopecia Tool (SALT) score for alopecia areata (AA).1Olsen E.A. Hordinsky M.K. Price V.H. et al.Alopecia areata investigational assessment guidelines – part II.J Am Acad Dermatol. 2004; 51: 440-447Abstract Full Text Full Text PDF PubMed Google Scholar We have updated this figure (SALT II) to include smaller increments of scalp coverage to facilitate the assessment of hair loss: (a) where small patches of hair loss predominate, such as in AA or cicatricial alopecia; and (b) where only certain areas of the scalp are involved, such as in male pattern hair loss (MPHL) and frontal fibrosing alopecia (FFA) (Fig 2). This reflects incorporation of earlier figures published by Olsen2Olsen E.A. Female pattern hair loss.J Am Acad Dermatol. 2001; 45: S70-S80Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar in 2001 and Olsen et al3Olsen E.A. Canfield D. Canfield W. Budris K. A novel method for assessing regional scalp hair density in male pattern hair loss.in: Van Neste D. Hair science and technology. Skininterface, Tournai (Belgium)2003: 251-254Google Scholar in 2003.Fig 2SALT II aid for determining scalp surface area more precisely. The SALT score, using either the original SALT I or SALT II, is determined by adding the percentage hair loss in the various areas of the scalp. With the addition of hair density, SALT II can also be used to establish patterns of hair loss germane to different hair loss conditions.View Large Image Figure ViewerDownload Hi-res image Download (PPT) To determine total and 1% SSA, we determined the head circumferences of 26 female [53-58 cm (mean 56 cm)] and 26 male [54.5-62 cm (mean 58 cm)] subjects. We then categorized the head circumference into small, medium, and large and measured the total SSA of 2 male subjects from each category. We used a conversion factor derived from these 6 male subjects to interpolate the SSA for the remaining subjects. The SSA results for all 52 subjects ranged from 607 cm2 (smallest head) to 842 cm2 (largest head) or an average of 705 cm2. In all, 1% of the SSA was approximately 7 cm2 with the sections of the SALT II diagram reflecting percentages of the total SSA, rounded to the nearest whole integer. These tools are analogous to the “rule of nines” and the palm plus 5 fingers used to determine percentage body surface area in various body regions in cutaneous lymphoma.4Olsen E.A. Vonderheid E. Pimpinelli N. Willemze R. Kim Y. Knobler R. et al.Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Study Group of the European Organization of Research and Treatment of Cancer (EORTC).Blood. 2007; 110: 1713-1722Crossref PubMed Scopus (1084) Google Scholar The new figure of the scalp can be used successfully to quantitate both total scalp hair loss or can be used specifically on one area of the scalp only, such as the central aspect of the scalp, to assess involvement of MPHL, female pattern hair loss (FPHL), and central centrifugal cicatricial alopecia (CCCA) or the frontal and temporal hair loss in FFA. Patterns of hair loss can also be defined with this figure for AA, MPHL, FPHL, CCCA, and FFA. Efficacy assessments can be done by noting the density in each of the areas of the involved scalp: for that purpose, we refer the reader to the method of combining region and density rating published on MPHL in 2003.3Olsen E.A. Canfield D. Canfield W. Budris K. A novel method for assessing regional scalp hair density in male pattern hair loss.in: Van Neste D. Hair science and technology. Skininterface, Tournai (Belgium)2003: 251-254Google Scholar We think this new tool will be extremely useful both in clinical practice and in clinical trials of hair loss. Given the new interest in treatments for AA, it is important to introduce this figure for potential use in Food and Drug Administration–sponsored studies for that hair loss condition in particular.

Diagnosis and treatment of Merkel Cell Carcinoma. European consensus-based interdisciplinary guideline

Merkel cell carcinoma (MCC) is a rare tumour of the skin of neuro-endocrine origin probably developing from neuronal mechanoreceptors. A collaborative group of multidisciplinary experts form the European Dermatology Forum (EDF), The European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on MCC diagnosis and management, based on a critical review of the literature, existing guidelines and expert’s experience. Clinical features of the cutaneous/subcutaneous nodules hardly contribute to the diagnosis of MCC. The diagnosis is made by histopathology, and an incisional or excisional biopsy is mandatory. Immunohistochemical staining contributes to clarification of the diagnosis. Initial work-up comprises ultrasound of the loco-regional lymph nodes and total body scanning examinations. The primary tumour should be excised with 1–2cm margins. In patients without clinical evidence of regional lymph node involvement, sentinel node biopsy is recommended, if possible, and will be taken into account in a new version of the AJCC classification. In patients with regional lymph node involvement radical lymphadenectomy is recommended. Adjuvant radiotherapy might be considered in patients with multiple affected lymph nodes of extracapsular extension. In unresectable metastatic MCC mono- or poly-chemotherapy achieve high remission rates. However, responses are usually short lived. Treatment within clinical trials is regarded as a standard of care in disseminated MCC.

Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing guidelines and the expert’s experience. The diagnosis of cSCC is primarily based on clinical features. A biopsy or excision and histologic confirmation should be performed in all clinically suspicious lesions in order to facilitate the prognostic classification and correct management of cSCC. The first line treatment of cutaneous SCC is complete surgical excision with histopathological control of excision margins. The EDF–EADO–EORTC consensus group recommends a standardised minimal margin of 5mm even for low-risk tumours. For tumours, with histological thickness of >6mm or in tumours with high risk pathological features, e.g. high histological grade, subcutaneous invasion, perineural invasion, recurrent tumours and/or tumours at high risk locations an extended margin of 10mm is recommended. As lymph node involvement by cSCC increases the risk of recurrence and mortality, a lymph node ultrasound is highly recommended, particularly in tumours with high-risk characteristics. In the case of clinical suspicion or positive findings upon imaging, a histologic confirmation should be sought either by fine needle aspiration or by open lymph node biopsy. In large infiltrating tumours with signs of involvement of underlying structures, additional imaging tests, such as CT or MRI imaging may be required to accurately assess the extent of the tumour and the presence of metastatic spread. Current staging systems for cSCC are not optimal, as they have been developed for head and neck tumours and lack extensive validation or adequate prognostic discrimination in certain stages with heterogeneous outcome measures. Sentinel lymph node biopsy has been used in patients with cSCC, but there is no conclusive evidence of its prognostic or therapeutic value. In the case of lymph node involvement by cSCC, the preferred treatment is a regional lymph node dissection. Radiation therapy represents a fair alternative to surgery in the non-surgical treatment of small cSCCs in low risk areas. It generally should be discussed either as a primary treatment for inoperable cSCC or in the adjuvant setting. Stage IV cSCC can be responsive to various chemotherapeutic agents; however, there is no standard regimen. EGFR inhibitors such as cetuximab or erlotinib, should be discussed as second line treatments after mono- or polychemotherapy failure and disease progression or within the framework of clinical trials. There is no standardised follow-up schedule for patients with cSCC. A close follow-up plan is recommended based on risk assessment of locoregional recurrences, metastatic spread or development of new lesions.

Diagnosis and treatment of dermatofibrosarcoma protuberans. European consensus-based interdisciplinary guideline

Dermatofibrosarcoma protuberans (DFSP) is a skin fibroblastic tumour that is locally aggressive, with a tendency for local recurrence, but rarely metastasizes. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on DFSP diagnosis and treatment, based on systematic literature reviews and the experts’ experience. Diagnosis is suspected clinically and confirmed by pathology. Analysis by fluorescence in situ hybridisation (FISH) or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) to detect specific chromosomal translocations and fusion gene transcripts is useful to confirm a difficult DFSP diagnosis. Treatment is mainly surgical, with the aim to achieve complete resection of the tumour. In order to reduce the recurrence rate, the treatment of choice of DFSP seems to be Mohs’ micrographic surgery (MMS) and related variants. In hospitals where only standard histopathological procedures are available, standard excision with lateral safety margin of 3cm is advisable. Imatinib (Glivec®) is approved in Europe for the treatment of inoperable primary tumours, locally inoperable recurrent disease, and metastatic DFSP. Imatinib has also been given to patients with extensive, difficult-to-operate tumours for preoperative reduction of tumour size, but the usefulness of this attitude should be confirmed by clinical trials. Therapeutic decisions for patients with fibrosarcomatous DFSP should be primarily made by an interdisciplinary oncology team (‘tumour board’).