Long-term Sequelae Of Treatment Research Articles

A multi-centre retrospective study of long-term outcomes of spinal re-irradiation with SABR.

Stereotactic ablative body radiotherapy (SABR) is a highly conformal technique utilising a high dose per fraction commonly employed in the re-treatment of spinal metastases. This study sought to determine the safety and efficacy of re-irradiation with SABR to previously treated spinal metastases. This was a retrospective analysis of patients at three Australian centres who have undergone spinal SABR after previous spinal radiotherapy to the same or immediately adjacent vertebral level. Efficacy was determined in terms of rates of local control, while safety was characterised by rates of serious complications. Thirty-three spinal segments were evaluated from 32 patients. Median follow-up for all patients was 2.6 years, and median overall survival was 4.3 years. Eleven of 33 (33.3%) treated spinal segments had local progression, with a local control rate at 12 months of 71.4% (95% C.I. 55.2%-92.4%). Four patients (16.7%) went on to develop cauda equina or spinal cord compression. Thirteen out of 32 patients (40.6%) experienced acute toxicity, of which 12 were grade 2 or less. Five out of 30 spinal (16.7%) segments with follow-up imaging had a radiation-induced vertebral compression fracture. There was one case of radiation myelitis which occurred in a patient who had mediastinal radiotherapy with a treatment field which overlapped their prior spinal radiation. The patients in this study experienced long median survival, durable tumour control and high rates of freedom from long-term sequelae of treatment. These results support the use of SABR in patients who progress in the spine despite previous radiotherapy.

Function Preservation in Head and Neck Cancers

The treatment of head and neck cancers can have a significant impact on function and appearance, which results in impairment of quality of life. Various long-term sequelae of treatment include speech and swallowing difficulty, oral incompetence, trismus, xerostomia, dental caries and osteoradionecrosis. Management has evolved from single modality treatment of either surgery or radiation to multimodality treatment to attain acceptable functional outcomes. Brachytherapy, also known as interventional radiotherapy, with its ability to deliver high doses centrally to the target, has been shown to improve local control rates. Due to the rapid fall-off of the dose of brachytherapy there is better organ at risk sparing as compared with that of external beam radiotherapy. In the head and neck region, brachytherapy has been practiced in various sites, including the oral cavity, oropharynx, nasopharynx, nasal vestibule and paranasal sinuses. Additionally, brachytherapy has also been considered for reirradiation as a salvage. Brachytherapy can also be considered as a perioperative technique together with surgery. Close multidisciplinary cooperation is required for a successful brachytherapy programme. In oral cavity cancers, depending on the location of the tumour, brachytherapy has been shown to preserve oral competence, maintain tongue mobility, maintain speech, swallowing and the hard palate. Brachytherapy in oropharyngeal cancers has been shown to reduce xerostomia and also reduce dysphagia and aspiration post-radiation therapy. For the nasopharynx, paranasal sinus and nasal vestibule, brachytherapy preserves the respiratory function of the mucosa. Despite such an incomparable impact on function and organ preservation, brachytherapy is an underutilised technique for head and neck cancers. There is a strong need to improve brachytherapy utilisation in head and neck cancers.

Finding a Needle in Haystack: Digital-PCR As a Sensitive Tool for MRD Detection in the Circulating-Tumor DNA Samples in Hodgkin Lymphoma

Introduction: Hodgkin lymphoma (HL) is the most frequent malignancy in young adults. The high probability of the cure is redeemed by both acute and long-term treatment sequelae. Balancing toxicity and efficacy requires highly reliable decision-making tools. Current treatment tailoring is based on the positron-emission tomography (PET/CT) assessment. The way how to improve the sensitivity of imaging methods could be a detection of minimal residual disease (MRD) in the circulating-tumor DNA (ctDNA) samples. The standard of the detection method is a next-generation sequencing (NGS), which covers a large spectrum of mutations, but is time-consuming, costly, and requires a significant concentration of ctDNA. The new digital PCR (dPCR) is a faster, cheaper method, which needs a lower amount of ctDNA. Aim: To validate the reliability of the dPCR for target-mutations of STAT6 and XPO1 genes detection in the peripheral blood ctDNA of patients with Hodgkin lymphoma Methods: CtDNA samples were obtained at the time of diagnosis/relapse, at the time of PET/CT assessment (interim, final), and during follow-up - every 3-6 months. CfDNA was extracted from peripheral blood plasma using the QiaAmp Circulating nucleic acid kit (Qiagen). Specific NGS panel covering coding sequences (including UTRs) of 13 selected genes (B2M, CD36, CIITA, GNA13, HIST1H1E, ITPKB, NFKBIE, PTPN1, SOCS1, SPEN, STAT6, TNFAIP3, and XPO1) was designed. For library preparation, we used SureSelect XT HS2 technology (Agilent Technologies) based on "target enrichment" with molecular barcodes. Sequencing was performed on a NovaSeq6000 (Illumina). Data were analyzed with the SureCall software (Agilent Technologies) with the sensitivity of 1.0% VAF. The detected variants were annotated using COSMIC, dbSNP, Ensembl, and ClinVar. Selected variants STAT6 p.N417Y and XPO1 p.E571K were further monitored by dPCR (QIAcuity Digital PCR System; Qiagen) with the sensitivity of 0.1% VAF. For dPCR experiments, we used a QIAcuityTM probe PCR kit (Qiagen) and nanoplate QIAcuity Nanoplate 26K 24-well (Qiagen). Primers and probes were taken and modified according to Camus et al., 2016 (EXPO1 p.E571K) and Spina et al., 2018 (STAT6 p.N417Y). All pts were analyzed with the same Siemens Biograph mCT scanner and results were independently reviewed by two physicians blinded for clinical outcome. Results: We have analyzed ctDNA using an NGS panel in 48 pts with CHL (44 at diagnosis, 4 in relapse). Mutations were detected in 22/48 (46%) pts. The most frequently mutated genes were STAT6 (12/48 pts), TNFAIP3 (10/48 pts), XPO1 (7/48 pts), and SOCS1 (7/26 pts). Frameshift deletions prevailed in TNFAIP3 and SOCS1 genes. Hotspot mutations in the STAT6 (p.N417Y, in five pts) and XPO1 (p.E571K, in six pts) genes we used as target mutations for dPCR cohort. The first date of ctDNA analysis was the first CHL diagnosis in ten and 1st relapse in one case. This dPCR-cohort (n=11) consists of 9 females and 2 males with a median age at the time of diagnosis of 40 yrs, with disease subtypes of nodular sclerosis (8), mixed-cellularity (1), lymphocyte-rich (1), and CHL unclassified (1). Mean VAF at diagnosis was 9.14% (0.76-25.0), mean cell-free DNA concentration 1.47 ng/mL (0.76-2.88). Three of the pts were considered to have intermediate and eight advanced cHL stages according to the GHSG system. Pts have received ABVD (n=5) or BEACOPPesc (n=5) or platinum-based+BEAM200 (n=1) protocols. Interim PET-2 was positive in 1 pt (stable disease), and final PET was positive in 2 (both PD). dPCR captured mutation in all three PETpos (0.12, 0.86, and 2.22%) cases, whereas was negative (<0.1% VAF) in all PETneg cases. During follow-up, two patients relapsed (both with detectable mutation, illustrative case is a Figure 1), in one case (pt during the BV post-ASCT maintenance) we observed transient dPCR positivity without evidence of relapse. Conclusion: A combination of the NGS (large-scale mutation screening) at the diagnosis with rapid and sensitive mutation monitoring using dPCR at the time of the treatment-tailoring or follow-up could improve decision-making accuracy in the routine care of Hodgkin lymphoma patients. Further analyses are needed to directly compare the sensitivity of the NGS and dPCR methods. Acknowledgement: Supported by MZCR-RVO (FNOL, 00098892) and AZV NU22-03-0018 grants. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NIMG-103. VOLUMETRIC CHANGES IN GRAY MATTER AFTER RADIOTHERAPY DETECTED WITH LONGITUDINAL MAGNETIC RESONANCE IMAGING IN GLIOMA PATIENTS

Abstract PURPOSE We evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volumetric reduction. METHODS A total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative radiotherapy (RT) was retrospectively analyzed. Study patients’ MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the ‘FastSurfer’ platform, a deep learning-based neuroimaging pipeline, a total of 73 subsites was automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Each subsite was grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of volumetric changes. RESULTS The median volumetric changes in the overall, ipsilateral, and contralateral GM were -3.5%, -4.5%, and -2.4% at 2 years after RT. The functional fields of cognition and execution of movement showed the greatest volumetric reductions. In the multivariable linear mixed model, female and the interaction between age and days after RT were significantly associated with GM volume reduction. The GM volume was significantly reduced in patients older than the subsite-specific threshold age at RT (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively). However, there was no significant GM volumetric reduction in patients younger than the threshold age at RT. CONCLUSIONS GM volumetric changes were identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed.

The role of primary dental care practitioners in the long-term management of patients treated for head and neck cancer

Patients treated for head and neck cancer may be susceptible to a higher incidence of dental disease due to long-term sequelae of treatment for head and neck cancer. Most patients with head and neck cancer are discharged from a hospital environment and responsibility for long-term dental care is transferred back from the restorative dentistry team to the dentist and dental care professionals in primary care. Treatment of these patients should be undertaken in a supportive environment, taking into account the physical and psychological repercussions of previous treatment. With the exception of some surgical procedures, routine dental care is not contraindicated in patients after head and neck cancer treatment and it is expected that the dentist and dental care professionals will be responsible for long-term routine dental treatment. Primary dental care practitioners should be aware of the process to refer patients back to the head and neck cancer multidisciplinary team if they note a suspicious change during their routine clinical examinations. Referral to a restorative dentistry consultant for planning and carrying out complex items of care may sometimes be necessary, but patients should always remain under the long-term care of their primary dental care practitioner.

Volumetric changes in gray matter after radiotherapy detected with longitudinal magnetic resonance imaging in glioma patients

Background and purposeWe evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volume reduction. Materials and methodsA total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative RT was retrospectively analyzed. Study patients’ MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the ‘FastSurfer’ platform, a deep learning-based neuroimaging pipeline, 73 regions were automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Regions were grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of significant volume reduction. ResultsThe median age was 50 years (range, 16–86 years). Forty-seven (44.8 %) patients were female and 68 (64.8 %) had glioblastoma. Postoperative RT was delivered at 54–60 Gy with or without concurrent chemotherapy. At 2 years after RT, the median volumetric changes in the overall, ipsilateral, and contralateral GM were −3.5%, −4.5%, and −2.4%, respectively. The functional fields of cognition and execution of movement showed the greatest volume reductions. In the multivariable linear mixed model, female sex (normalized coefficient = −0.14, P < 0.001) and the interaction between age at RT and days after RT (normalized coefficient = −6.48e-6, P < 0.001) were significantly associated with GM reduction. The older patients received RT, the greater volume reduction was seen over time. However, in patients with relatively younger age (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively), the volume was not significantly reduced. ConclusionsGM volume reduction was identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed.

Cancer treatment-related cardiac dysfunction

ObjectivesThis paper describes cardiotoxicity and cancer treatment-related cardiac dysfunction (CTRCD). Long-term sequelae of treatment are important, and changing, and may manifest when a patient is under the care of a...

Assessing radiation-induced carotid vasculopathy using ultrasound after unilateral irradiation: a cross-sectional study

BackgroundIncreased head and neck cancer (HNC) survival requires attention to long-term treatment sequelae. Irradiated HNC survivors have a higher ischemic stroke risk. However, the pathophysiology of radiation-induced vasculopathy is unclear. Arterial stiffness could be a biomarker. This study examined alterations in intima-media thickness (IMT) and stiffness-related parameters, shear wave (SWV) and pulse wave velocity (PWV), in irradiated compared to control carotids in unilateral irradiated patients.MethodsTwenty-six patients, median 40.5 years, 5–15 years after unilateral irradiation for head and neck neoplasms underwent a bilateral carotid ultrasound using an Aixplorer system with SL18-5 and SL10-2 probes. IMT, SWV, and PWV were assessed in the proximal, mid, and distal common (CCA) and internal carotid artery (ICA). Plaques were characterized with magnetic resonance imaging. Measurements were compared between irradiated and control sides, and radiation dose effects were explored.ResultsCCA-IMT was higher in irradiated than control carotids (0.54 [0.50–0.61] vs. 0.50 [0.44–0.54] mm, p = 0.001). For stiffness, only anterior mid-CCA and posterior ICA SWV were significantly higher in the irradiated side. A radiation dose–effect was only (weakly) apparent for PWV (R2: end-systolic = 0.067, begin-systolic = 0.155). Ultrasound measurements had good–excellent intra- and interobserver reproducibility. Plaques had similar characteristics but were more diffuse in the irradiated side.ConclusionsIncreased CCA-IMT and SWV in some segments were seen in irradiated carotids. These alterations, even in young patients, mark the need for surveillance of radiation-induced vasculopathy.Trial registration: clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04257968).

Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: A contemporary single-institution experience.

Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity. A single-center, retrospective study was conducted of patients age ≥18 years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses. Fifty-nine patients met criteria, with median age of 25 years (range 18-62 y) and median follow-up of 6.5 years (range 0.7-23.1 y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6 Gy (relative biological effectiveness [RBE]), median total dose was 54.0 Gy (RBE), 80% received proton radiotherapy; 81% received chemotherapy. 5 year PFS and OS were 86.5% and 95.8%, respectively; 10 year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (P = .04). Among eight recurrences, 25% presented after 5 years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (P = .05). Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae.

Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer

Cervical cancer survivors report the worst quality of life (QoL) among all cancer survivors and this is mainly due to their younger age and the long-term treatment sequelae. The purpose of this study is to assess the long-term QoL and sexual function of locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemotherapy (NACT) and radical hysterectomy (RH) instead of the standard chemoradiotherapy. This is a retrospective case-control study including LACC patients (FIGO stage IIB-IVA) treated with the NACT-RH strategy and a control group of healthy women undergoing hysterectomy for uterine fibromatosis in the same period. Main outcome measures were the EORTC QLQ-C30 and EORTC QLQ-CX24 for quality of life and Female Sexual Function Index (FSFI) for sexual function. Overall, 96 patients were included: 48 LACC and 48 controls. The mean age at diagnosis was 45.5 ± 9.0 and 47.0 ± 7.8, respectively (P=.38). Compared to controls, LACC patients reported lower mean scores for the global health status (69.4 ± 22.6 vs 81.2 ± 24.3; Mean Difference (MD): -11.80 [95% CI: -21.19, -2.41]; P=.016), QLQ-C30 functional scale (80.1 ± 22.6 vs 92.4 ± 14.9; MD: -12.30 [95% CI: -19.96, -4.64]; P=.002), QLQ-Cx24 functional scale (55.5 ± 25.0 vs 80.4 ± 22.4; MD: -24.00 [95% CI: -34.40, -15.40]; P < .001), and the total FSFI (19.3 ± 9.6 vs 26.2 ± 9.9; MD: -6.90 [95% CI: -10.80, -3.00]; P < .001). On the other hand, LACC patients reported higher mean scores on the QLQ-C30 (16.9 ± 22.1 vs 8.4 ± 16.6; MD: 8.50 [95% CI: 0.68, 16.32]; P=.03) and QLQ-CX24 (26.0 ± 28.8 vs 15.0 ± 11.7; MD: 11.00 [95% CI: -2.21, 19.79]; P=.01) symptoms scales. The confirmed poor quality of life even in surgically treated LACC survivors underlines the importance of tailoring parametrectomy based on lymph node status and developing personalized strategies. The study assessed the long-term QoL and sexual function in the specific subpopulation of LACC patients treated with NACT-RH. Main limitations include the small sample size and the retrospective design. LACC long-term survivors treated with NACT-RH experience poor QoL and sexual dysfunction. Palaia I, Santangelo G, Caruso G, et al. Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer. J Sex Med 2022;19:613-619.

Sexual and urinary dysfunction after proctectomy with or without abdominoperineal resection: Incidence and treatment

As oncologic outcomes of rectal cancer treatment continue to improve, there has been an increased focus on the quality of life of survivors, including urinary and sexual function. Given its profound impact, it is imperative to have a better understanding of urogenital dysfunction in this context in order to advance new therapies and promote patient rehabilitation. Clinicians should focus on broad preoperative counseling and postoperative interventions to counterbalance the negative impact of surgery and radiotherapy. Clinicians should be aware that although rectal cancer may be cured, long-term treatment sequelae may persist.

Subsequent Anal Malignancies In Patients With Prostate Adenocarcinoma Treated With Brachytherapy Or External Beam Radiotherapy Compared With Surgery

It is important to understand the potential long-term sequelae of treatment of prostate adenocarcinoma, as patients are being diagnosed at a younger age and surviving longer. The risk of subsequent malignancies after brachytherapy (BT) has been reported to be low due to the limited exposure of normal tissue to radiation given the rapid dose fall off. However, our clinical experience suggested an increased risk of subsequent anal malignancy in patients receiving prostate BT. This risk may have implications for post-treatment surveillance. Therefore, we sought to compare the risk of subsequent anal malignancy after BT or external beam radiotherapy (EBRT) compared to surgery for prostate adenocarcinoma. Data regarding the rate of incidence from the Surveillance, Epidemiology, and End Results Program cancer registry (1988–2016) were used to directly compare subsequent anal malignancy risk in men with prostate adenocarcinoma treated with BT or EBRT versus surgery alone using two-sided Poisson exact rate ratio tests. We also compared risks in patients whose follow up time since prostate cancer diagnosis was ≥ 5 years. The year 1988 represents the first year in which radiotherapy modality (EBRT versus BT) was reported. Directly comparing the risks in each radiotherapy group with the surgery group helps to avoid problems associated with underreporting subsequent malignancies. Subsequent anal malignancies developed in 12 of 25,011 men with prostate adenocarcinoma who received BT, 28 of 65,353 who underwent EBRT, and 10 of 85,868 men who underwent surgery. BT was associated with a statistically significant increase in the risk of subsequent anal cancer (rate ratio (RR) 3.83 [95% confidence interval (CI): 1.52, 9.90] relative to surgery; P = 0.004). EBRT for prostate adenocarcinoma was also associated with a statistically significant increase in the risk of subsequent anal cancer (RR 3.39 [95 % CI: 1.60, 7.81] relative to surgery; P < 0.001). Among patients whose follow up time since prostate cancer diagnosis was ≥ 5 years, EBRT was not associated with an increased risk of subsequent anal cancer (RR 2.66 [95% CI: 0.87, 9.64] relative to surgery; P = 0.09); however, BT was associated with a statistically significant increase in the risk of subsequent anal cancer (RR 5.03 (95% CI: 1.45 – 19.53) relative to surgery; P = 0.009). Both BT and EBRT for prostate adenocarcinoma were associated with a statistically significant enhancement in the risk of subsequent anal cancers. While subsequent anal cancers occurred rarely, the increased risk of subsequent anal cancers after prostate BT, especially in those with follow up ≥ 5 years after prostate cancer diagnosis, may have implications for surveillance after treatment.

How I Treat Medulloblastoma in Children

AbstractMedulloblastoma (MB) is the most common malignant tumor of the central nervous system in children with up to a third of these tumors presenting in children under 3 years of age. Its exquisite radio and chemosensitivity renders high cure rates in children in whom optimal resection has been achieved. Optimal surgery followed by radiation alone can cure about half of these children. The addition of chemotherapy has improved the outcomes dramatically and over 70% of children over 3 years of age with optimal resection and no metastasis can expect to be cured. Increasingly, the focus is on limiting the long-term sequelae of treatment. Precise molecular characterization can enable us to identify patients who can achieve optimal outcomes even in the absence of radiation. Insights into disease biology and molecular characterization have led to dramatic changes in our understanding, risk stratification, prognostication, and treatment approach in these children. In India, there is limited access to molecular profiling, making it challenging to apply biology driven approach to treatment in each child with MB. The Indian Society of Neuro-Oncology guidelines and the SIOP PODC adapted treatment recommendations for standard-risk MB based on the current evidence and logistic realities of low-middle income countries are a useful adjunct to guide clinical practice on a day-to-day basis in our setting.

Grommets in otitis media: a 25-year follow up

Background: This study is unique as it is the first study which can describe the long term sequelae of treatment of otitis media with effusion (OME) with insertion of grommets in the Primary Health Sector in Denmark.Objectives: Eardrum pathology and hearing acuity 25 years after treatment of OME by insertion of grommets, in a private ear-, nose-, and throat practice.Material and methods: 262 children with OME were treated from 1975 to 1978. The patients were re-examined by otomicroscopy, tympanometry and pure tone audiometry after 7.5, 12, and 25 years.Results: Hearing level, flaccida retraction and incudo pexi was equivalent. For atrophy and myringosclerosis no equivalence was shown using 95% confidence intervals. Tympanometry was fairly unchanged.Conclusion and significance: The insertion of a grommet in treating OME has no influence on hearing acuity in the long term. The prevalence of myringosclerosis and atrophy was unchanged in 70–80% of the eardrums. Most important is that the small increase in myringosclerosis and atrophy does not seem to influence the hearing acuity. We show that long term sequelae from the Primary Health Sector are similar to those from the Secondary Health sector.

Symptomatic osteonecrosis as a treatment complication in Hodgkin lymphoma: an analysis of the German Hodgkin Study Group (GHSG).

The majority of patients with Hodgkin Lymphoma (HL) can be cured with stage and risk adapted treatment today. Therefore, current research focuses on reducing long-term sequelae of treatment. Osteonecrosis (ON) is a severe long-term complication of HL treatment which has so far not been systematically evaluated. Hence, we investigated incidence, risk factors and timing of symptomatic ON in HL patients. Further endpoints included localization, intervention and outcome of ON. We included all qualified HL patients of the randomized German Hodgkin Study Group trials HD10-15 and HD18, recruited between 05/1998 and 07/2014 and aged from 16 to 60 years. Among 11 330 patients, 66 developed symptomatic ON after first-line treatment, 83.3% within three years. The incidence of symptomatic ON was 0.2% in early-stage HL and 1.0% in advanced-stage HL. Logistic regression revealed the total cumulative corticosteroid dose to be a strong risk factor interacting with younger age. Male sex additionally increased the risk of symptomatic ON. The prognostic value of the corresponding logistic regression model was rather high (AUC = 0.78). Other tested potential risk factors including obesity, IPS and radiotherapy did not further increase the risk of ON. Further development of current treatment protocols should aim to reduce the cumulative corticosteroid dose.

Oral Cancer.

The management of oral cancer is a multidisciplinary endeavour, as each patient presents the treating clinicians with a unique set of challenges the management of which impacts on both survival and quality of life. This article focuses on the management of oral cancer. We highlight the epidemiology and risk factors for oral cancer in Australia, the various clinical presentations that occur and the staging of oral cancer. In the vast majority of cases surgery remains the mainstay of treatment. Radiation and medical oncology is usually used in an adjuvant context. Dental professionals play a critical role in many stages of management from the initial detection, to optimising pre treatment dental health and managing the short and long term sequelae of treatment. Monitouring for recurrence and the development of second primary tumours is a key role.

The women in steady exercise research (WISER) survivor trial: The innovative transdisciplinary design of a randomized controlled trial of exercise and weight-loss interventions among breast cancer survivors with lymphedema

IntroductionBreast cancer survivors face dual challenges: long term sequelae of treatment, and risk of recurrent disease. Obesity and a sedentary lifestyle complicate both challenges. The WISER Survivor trial assessed the effects of exercise and/or weight-loss on lymphedema, biomarkers of breast cancer recurrence, and quality of life. We report on the innovative transdisciplinary design of this trial and report attrition rates. MethodsThis one year trial randomized breast cancer survivors who had a BMI of ≥25kg/m2, were sedentary and had breast-cancer-related-lymphedema to 1) exercise (weight training and aerobic exercise) 2) weight-loss 3) exercise and weight-loss 4) or control group. Innovative aspects included: adaptation of a community-based weight training program to a largely home-based program; use of a commercial meal replacement system as part of the lifestyle modification weight-loss program; inclusion of measures of cost-effectiveness to enable economic evaluations; and alignment with a parallel mouse model for breast cancer recurrence to enable transdisciplinary research. In this model, mice bearing dormant residual tumor cells, which spontaneously relapse, were placed on a high-fat diet. Overweight animals were randomly assigned to exercise, calorie restriction, both, or control group and followed for cancer recurrence. The animal model will guide mechanistic biomarkers to be tested in the human trial. Results & discussion351 participants were randomized; 13 experienced breast cancer recurrence during the trial. Of the 338 participants without recurrence, 83% completed the trial. The WISER Survivor trial will show the effects of exercise and weight-loss on lymphedema outcomes, biomarkers of recurrence and quality of life.NCT ClinicalTrials.gov registration #: NCT01515124

Prospective surveillance using l-dex monitoring results in significant reductions in the chronic rate of breast cancer related-lymphedema (BCRL) in high-risk breast cancer patients.

118 Background: Survivorship represents an increasing focus in the management of breast cancer with chronic toxicities including breast cancer-related lymphedema (BCRL). This study looked at prospective surveillance using bioimpedance spectroscopy (BIS) to reduce risks of chronic BCRL requiring referral for complete decongestive therapy (CDT). Methods: 132 patients at high-risk for the development of BCRL were prospectively followed using BIS with serial monitoring. This included a pre-operative baseline assessment and a minimum of two post-operative follow up assessments. Interventions were initiated when the L-Dex score increased by greater than 10 units from baseline and consisted of conservative treatment with a compression sleeve for four weeks. Patients were also clinically monitored for the development of BCRL. Results: Median follow-up was 19.3 months (range 4-54 mos). Of the 132 patients evaluated, 24 (18.1%) were subsequently diagnosed with elevated L-Dex scores and underwent intervention. Of the 24 that underwent treatment, 14 (58%) had resolution of their elevated L-Dex scores following four weeks of therapy with 10 having persistent elevations and clinical BCRL which necessitated referral to physical therapy for CDT. A further 7 subjects were diagnosed and not treated for elevated L-Dex scores, but had complete resolution (return to baseline) at last visit. At last follow-up, only 10 patients (7.6 %) had unresolved, clinical stage 1, BCRL. Conclusions: The use of L-Dex to prospectively follow our high-risk patients and prescribe intervention with a compression sleeve for 4 weeks when scores are elevated resulted in only a 7.6 % rate of stage 1, chronic BCRL. This rate of BCRL has been reported as 15-20%, suggesting that a prospective program of screening and intervention using L-Dex does result in clinically meaningful reductions in this long-term sequelae of treatment.

PPAC (programme personnalisé de l’après-cancer) : rationnel et mise en place

The growing number of breast cancer survivors challenges healthcare organizations, particularly oncology specialty and primary care providers. Currently, in France, the follow-up care is based on detection of recurrences, of second primary contralateral breast cancer, of long-term treatment sequelae, in addition to psychosocial consequences of cancer and its treatment. This review will discuss the evidence base and intents of breast cancer survivorship care plans (CSCPs) as a wellness model for cancer survivors in clinical setting, mainly providing health promotion recommendations such as regular exercise. The CPCPs involve multidisciplinary approach and patient–physician communication. Therefore, this comprehensive care will improve their quality of life, treatment compliance, and general health care maintenance. This article offers innovative guidance to implement the post-cancer patient care and includes the relevant templates to be submitted to the patients.

Managing teenage/young adult (TYA) brain tumors: a UK perspective

Tumors of the CNS are among the commonest malignancies occurring in teenage/young adult patients (i.e., those aged between 15 and 24 years). The treatment of this patient population is challenging. Adolescence and young adulthood are a turbulent period of life, with physical, emotional, social and cognitive changes. Best practice advocates their treatment in dedicated teenage/young adult units, with multidisciplinary team input and access to clinical trials. Treatment of CNS malignancies is dependent upon histological subtype and staging, with varying combinations of surgery, radiotherapy and chemotherapy used. Clinical trials directly targeted at this patient population are rare; treatments are based on pediatric protocols as studies have demonstrated improved outcomes in patients (with other malignancies) treated as such. Scope for improvement lies in minimizing patient risk of recurrence and long-term sequelae of treatment. Molecular characterization of tumors may provide further information.