Locoregional Tumor Control Research Articles

Imaging of Radiation Treatment of Lung Cancer

Radiation therapy is an important modality in the treatment of patients with lung cancer. Recent advances in delivering radiotherapy were designed to improve loco-regional tumor control by focusing higher doses on the tumor. More sophisticated techniques in treatment planning include 3-dimensional conformal radiation therapy, intensity-modulated radiotherapy, stereotactic body radiotherapy, and proton therapy. These methods may result in nontraditional patterns of radiation injury and various radiologic appearances that can be mistaken for recurrence, infection and other lung diseases. Knowledge of radiological manifestations, awareness of new radiation delivery techniques and correlation with radiation treatment plans are essential in order to correctly interpret imaging in these patients.

Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma

ObjectivesRandomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response. Materials and methodsCases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups. ResultsWe identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings. ConclusionWhen treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC.

Анализ результатов рандомизированных исследований по гипертермии в онкологии

The review presents statistics of published randomized phase III trials on the addition of hyperthermia (HT) to other cancer therapies, and analyzes the results of these trials. In total, 47 comparisons could be made for treatments with or without HT. These trials were done in a large variety of solid tumors, and in centers in Asia, Europe, North America and Australia. In general, these studies were relatively small – 17 studies included more than 100 patients. The total number of patients was 5099. In the majority of the studies, HT was applied with electromagnetic radiation. Most studies (74 %) have shown that additional HT significantly improves the results of radiation, chemo- and chemoradiotherapy in patients with, in general, locally advanced relapsed and metastatic forms of malignant tumors. Improved results were reported for complete and overall response, loco-regional tumor control, disease free and overall survival, and, in one study, for palliative effects. In these randomized trials also acute and/or late toxicity has been investigated. In the majority of the trials, addition of HT did not result in significant increases of toxic effects. The economic consequences of HT as part of cancer treatment are discussed. Twenty-six percent of the studies failed to show a significant beneficial effect of HT which are discussed in more detail. In 4 studies with a trend of a better outcome in the plus HT treatment arm, with an absolute difference of 10 % or more, the lack of significance is probably due to a low number of patients included. In other studies, there was an unbalanced distribution of tumor characteristics over the two study arms, with worse prognostic factors in the plus HT arm, inadequate techniques, using too high frequency of electromagnetic radiation, and/or a small applicator, and/or a short heating time, so that a sufficient energy deposition in the tumor volume could not be achieved. These results make clear that it is important to develop guidelines for the application of HT, in addition to the existing ones. In view of the different principles of operation of HT applicators, it is important that such guidelines will become available for each individual device. Further, it is important to conduct larger randomized trials. Larger studies would probably increase the number of significant and also more relevant outcomes, and promote a wider acceptance of HT as part of cancer treatment.

A comparative study of hypofractionated and conventional radiotherapy in postmastectomy breast cancer patients

Objective:The aim of this study was to compare toxicity and locoregional control of short duration hypofractionated (HF) radiotherapy (RT) with conventional RT in breast cancer patients.Methods:A total of 100 postmastectomy breast cancer patients were randomized for adjuvant RT in control group (comprising fifty patients who received the standard conventional dose of 50 Gy in 25 fractions with 2 Gy per fraction) and study group (comprising fifty patients who received HF RT with dose of 42.72 Gy in 16 fractions with 2.67 Gy per fraction). All patients were treated on linear accelerator with 3-dimensional conformal RT technique. Outcome was analyzed in terms of toxicity, tolerability, and locoregional control.Results:In the present study, at a median follow-up of 20 months, almost similar results were seen in both the groups in terms of toxicity, tolerability, and locoregional control. Adjuvant postmastectomy HF RT was found to be well tolerated with mild-to-moderate side effects that neither reached statistical significance nor warranted any treatment interruption/hospitalization.Conclusions:HF postmastectomy RT is comparable to conventional RT without evidence of higher adverse effects or inferior locoregional tumor control and has an added advantage of increased compliance because of short duration; hence, it can help in accommodating more breast cancer patients in a calendar year, ultimately resulting in decreased waiting list, increased turnover, and reduced cost of treatment.

PORTAF \u2013 postoperative radiotherapy of non-small cell lung cancer: accelerated versus conventional fractionation \u2013 study protocol for a randomized controlled trial

BackgroundIn early-stage non-small cell lung cancer (NSCLC) without affected lymph nodes detected at staging, surgical resection is still the mainstay of treatment. However, in patients with metastatic mediastinal lymph nodes (pN2) or non-radically resected primary tumors (R1/R2), postoperative radiotherapy (possibly combined with chemotherapy) is indicated. So far, investigations about time factors affecting postoperative radiotherapy have only examined the waiting time defined as interval between surgery and start of radiotherapy, but not the overall treatment time (OTT) itself. Conversely, results from trials on primary radio(chemo)therapy in NSCLC show that longer OTT correlates with significantly worse local tumor control and overall survival rates. This time factor of primary radio(chemo)therapy is thought to mainly be based on repopulation of surviving tumor cells between irradiation fractions. It remains to be elucidated if such an effect also occurs when patients with NSCLC are treated with postoperative radiotherapy after surgery (and chemotherapy). Our own retrospective data suggest an advantage of shorter OTT also for postoperative radiotherapy in this patient group.Methods/designThis is a multicenter, prospective randomized trial investigating whether an accelerated course of postoperative radiotherapy with photons or protons (7 fractions per week, 2 Gy fractions) improves locoregional tumor control in NSCLC patients in comparison to conventional fractionation (5 fractions per week, 2 Gy fractions). Target volumes and total radiation doses will be stratified in both treatment arms based on individual risk factors.DiscussionFor the primary endpoint of the study we postulate an increase in local tumor control from 70% to 85% after 36 months. Secondary endpoints are overall survival of patients; local recurrence-free and distant metastases-free survival after 36 months; acute and late toxicity and quality of life for both treatment methods.Trial registrationClinicalTrials.gov, NCT02189967. Registered on 22 May 2014.

A comparative study of machine learning methods for time-to-event survival data for radiomics risk modelling

Radiomics applies machine learning algorithms to quantitative imaging data to characterise the tumour phenotype and predict clinical outcome. For the development of radiomics risk models, a variety of different algorithms is available and it is not clear which one gives optimal results. Therefore, we assessed the performance of 11 machine learning algorithms combined with 12 feature selection methods by the concordance index (C-Index), to predict loco-regional tumour control (LRC) and overall survival for patients with head and neck squamous cell carcinoma. The considered algorithms are able to deal with continuous time-to-event survival data. Feature selection and model building were performed on a multicentre cohort (213 patients) and validated using an independent cohort (80 patients). We found several combinations of machine learning algorithms and feature selection methods which achieve similar results, e.g., MSR-RF: C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with Spearman feature selection. Using the best performing models, patients were stratified into groups of low and high risk of recurrence. Significant differences in LRC were obtained between both groups on the validation cohort. Based on the presented analysis, we identified a subset of algorithms which should be considered in future radiomics studies to develop stable and clinically relevant predictive models for time-to-event endpoints.

Regional Neck Control in Head and Neck Squamous Cell Carcinoma with Positive Neck Disease Treated with Primary Chemoradiation

The treatment of squamous cell carcinomas of the head and neck (HNSCC) is multidisciplinary. Chemoradiation has become an integral part of the treatment process in managing metastatic neck disease. Randomized controlled trials and meta-analyses have demonstrated major improvements not only in loco-regional tumor control, but also in terms of survival when chemotherapy is added to radiotherapy. In clinical practice, this has translated into a reduction in the number of recurrent neck disease needing salvage surgery. Studies have reported up to 2-year overall survival (OS) of 92% and disease-free survival (DFS) of 95%, in patients with advanced HNSSC treated with CRT. This single institution, retrospective cohort study was conducted to analyze the regional control rates after primary chemo-radiation therapy in a tertiary center.

Residual tumour hypoxia in head-and-neck cancer patients undergoing primary radiochemotherapy, final results of a prospective trial on repeat FMISO-PET imaging

BackgroundHypoxia is a well recognised parameter of tumour resistance to radiotherapy, a number of anticancer drugs and potentially immunotherapy. In a previously published exploration cohort of 25 head and neck squamous cell carcinoma (HNSCC) patients on [18F]fluoromisonidazole positron emission tomography (FMISO-PET) we identified residual tumour hypoxia during radiochemotherapy, not before start of treatment, as the driving mechanism of hypoxia-mediated therapy resistance. Several quantitative FMISO-PET parameters were identified as potential prognostic biomarkers. Here we present the results of the prospective validation cohort, and the overall results of the study. MethodsFMISO-PET/CT images of further 25 HNSCC patients were acquired at four time-points before and during radiochemotherapy (RCHT). Peak standardised uptake value, tumour-to-background ratio, and hypoxic volume were analysed. The impact of the potential prognostic parameters on loco-regional tumour control (LRC) was validated by the concordance index (ci) using univariable and multivariable Cox models based on the exploration cohort. Log-rank tests were employed to compare the endpoint between risk groups. ResultsThe two cohorts differed significantly in several baseline parameters, e.g., tumour volume, hypoxic volume, HPV status, and intercurrent death. Validation was successful for several FMISO-PET parameters and showed the highest performance (ci=0.77–0.81) after weeks 1 and 2 of treatment. Cut-off values for the FMISO-PET parameters could be validated after week 2 of RCHT. Median values for the residual hypoxic volume, defined as the ratio of the hypoxic volume in week 2 of RCHT and at baseline, stratified patients into groups of significantly different LRC when applied to the respective other cohort. ConclusionOur study validates that residual tumour hypoxia during radiochemotherapy is a major driver of therapy resistance of HNSCC, and that hypoxia after the second week of treatment measured by FMISO-PET may serve as biomarker for selection of patients at high risk of loco-regional recurrence after state-of-the art radiochemotherapy.

Improved survival with postoperative radiotherapy in thymic carcinoma: A propensity-matched analysis of Surveillance, Epidemiology, and End Results (SEER) database

ObjectivesThymic carcinoma is a rare and aggressive malignancy with poor prognosis. Although postoperative radiotherapy (PORT) is used for obtaining better locoregional tumor control, its association with survival has not been established. This study evaluated the prognostic impact of PORT in thymic carcinoma. Materials and methodsWe identified patients diagnosed with thymic carcinoma between 2004 and 2013 using the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching with Kaplan-Meier and Cox-regression analyses were used to assess prognosis. ResultsIn the unmatched population (n=312), 184 (59%) patients underwent PORT. The 5-year overall survival rates were better with receipt of PORT, both before and after matching (P=0.012 and 0.007, respectively). After adjusting for related covariates (n=256), age ≥63 years (P=0.023), Masaoka stage III (P=0.028) and IV (P<0.001), debulking surgery (P=0.021), and no receipt of PORT (P=0.013) were independently poor prognostic factors. In subgroup analyses, favorable survival impacts of PORT were observed for Masaoka stage III tumors (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.15–0.66), tumors sized >6.0cm (HR 0.48, 95% CI 0.26–0.89), node-negative status (HR 0.58, 95% CI 0.33–1.00), and surgical extent of local excision or partial removal (HR 0.44, 95% CI 0.22–0.86). ConclusionOn SEER analysis, survival benefits of PORT in thymic carcinoma were demonstrated. With strong prognostic associations of Masaoka stage and types of surgery, PORT should be considered for non-metastatic locally advanced tumors with limited surgical resection.

Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol

BackgroundStandard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation.MethodsThe ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1st and 5th week (cisplatin 20 mg/m2/d d 1–5 and d 29–33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start.DiscussionThe primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1.Trial registrationClinicalTrials.gov Identifier: NCT 01212354, EudraCT-No.: 2010-021139-15

Radiolabeled Immunoglobulin Therapy for Patients with Solid Tumors

Purpose: To test the reactivity of monoclonal murine IgM and IgG for Tenascin-C (TNC) in formalinized solid human tumors tissue samples and to estimate the radiation dose that Yttrium- 90 labeled murine IgM reactive with TNC can deliver to a solid tumor and tumor containing draining lymph nodes. Materials and Methods: Using Immunohistochemistry (IHC), mouse anti-human TNC IgM and IgG clones were tested for the detection of TNC in formalin fixed biopsies of patients with Glioblastoma multiforme (GBM), adeno carcinoma of the exocrine pancreas (PaCa)-, breast-, colon-, renal-, ovary- prostate carcinoma, cutaneous-, ocular- melanomas, and Ewing Sarcoma. IHC was performed on all tumors with an n=1, except for PaCa and ocular melanomas, n=11. Monte-Carlo simulation and convolution calculations were used to determine the activity of Y-90 required for delivering 100Gy to a 50 × 50 × 50 mm3 water-equivalent tumor model, assuming a homogeneous distribution of the radioimmunoconjugate throughout the model volume. Results: IHC has confirmed reactivity of IgM with TNC in all of the tested human solid tumors samples except for ocular melanoma. Positive and negative controls of IgM specificity were used. The dosimetry simulation predicted an Yttrium-90 activity of 217 MBq to deliver a dose of 100Gy to the tumor model with a 6 mm sharp dose fall off in surrounding normal tissues. Conclusion: Loco-regional control of human solid tumors may be obtained with intra-tumoral administration of radiolabeled IgM targeting TNC. In TNC negative solid tumors such as ocular melanoma, other tumor-specific target(s) need to be identified.

Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?

PurposePostmastectomy chest wall radiation therapy has historically used bolus to increase dose at the skin surface. Despite the theoretical benefits of bolus, the clinical implications of locoregional tumor control, cosmesis, and the incidence of radiodermatitis are less well characterized. We hypothesized that treatment in the presence or absence of bolus results in equivalent chest wall recurrence rates, but its presence results in more severe acute dermatologic toxicity. Methods and materialsLocally advanced breast cancer patients undergoing chest wall radiation therapy were retrospectively reviewed from 2005 to 2015 (n = 106; 53 with bolus, 53 without). Outcomes including local failure, acute skin toxicity, and treatment interruptions were recorded. Median age was 59 years (range, 28-91) and median follow-up was 34 months. Histology was invasive ductal carcinoma (73%), invasive lobular carcinoma (20%), inflammatory (6%), and neuroendocrine (1%). Fifty-nine percent were T3/T4 primary tumors and 29.2% had clinical/pathologic skin involvement. Node-positive patients accounted for 80.2%. Chemotherapy was administered in 84.0%. All patients had 3-dimensional conformal radiation therapy and received a median dose of 61Gy (range, 50-63 Gy). ResultsLocal failure was 6.6% (n = 7) overall, with 4 failures in the bolus group and 3 in the no bolus group. No pathological factors were associated with local failure. Acute grade 2 and 3 skin toxicities (37 vs 22) and treatment interruptions (20 vs 3) were more common in the bolus group (P < .05). Mean treatment interruption (14.5 vs 5 days) was longer for patients receiving bolus. Patients undergoing treatment interruption were more likely to fail locally than patients not requiring a treatment interruption (17.4% vs 3.6%, P = .0322). ConclusionsBolus omission in adjuvant chest wall radiation therapy may be a reasonable approach to avoid acute skin toxicity and treatment interruptions while preserving local control; however, further study will be needed to reach a definitive conclusion.

1008P - Effect of protracted radiotherapy treatment on outcome of head and neck SCC patients (NEMROCK experience)

Patients with head and neck cancer receiving radiation therapy alone or with concurrent chemotherapy often develop mucositis that may lead to unplanned treatment interruptions, these decreases in treatment intensity may reduce rates of loco-regional tumor control and survival. A total number of one hundred twenty head and neck cancer patients included in this retrospective study presented to NEMROCK between January 2005 and December 2010 after they underwent surgery and received their post operative adjuvant radiotherapy with or without concomitant chemotherapy. The impact of both overall treatment time of radiation and treatment gaps on loco regional tumor control and overall survival were studied. Radiation treatment gaps lasting 5 days or less did not influence LC (86%) at 3-years, which may suggest that the average dose intensity (>9 Gy/week), appeared high enough to compensate for few days of treatment break meanwhile patients received low DI (<9 Gy/week) had three times risk of recurrence (HR = 3.13; 95% CI, 1.47-6.64; p = 0.003). However prolongation of treatment gaps more than 10 days are related to a decrease in 3-years LCR to 40% (from 86% to 46% p = 0.001). Similar statistically significant difference in 3 years OAS was also observed among the patients with no or up to 5 days treatment gap and the patients experienced > 10 days gap (87.8% vs. 61%, p = 0.001). An increased OTT (> 60 days) and low DI (9 Gy/week) are seem to be related to a decreased OAS among our patients in multivariate analysis. In this retrospective study, patients with head-and-neck cancer, who have unplanned interruptions in radiotherapy have an increased risk of death and tumor recurrence. This analysis have several limitations. It is impossible to fully remove the effect of unmeasured factors that are associated both with presence of treatment interruptions and risk of death like mucositis, xerostomia, dysphagia, and aspiration, each of which may also be associated with decreased survival time. Thus, the observed increased risk of death associated with interruptions in radiotherapy may not be entirely attributable to the interruptions themselves.

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(-) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG.

To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control. Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P = 0.010) or the 26-gene signature (P = 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P = 0.006; 26-gene signature: HR 10.27, P = 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P = 0.016; SLC3A2: HR 8.54, P = 0.037; CD44: HR 3.36, P = 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup. We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies. Clin Cancer Res; 22(11); 2639-49. ©2016 AACR.

The ratio of CD4/CD8 T-cells in human papillomavirus-positive laryngeal squamous cell carcinoma accounts for improved outcome

Conclusion: Improved prognosis associated with HPV-positive status may depend on lower CD4/CD8 ratio. Th1 CD4+ T cells were found to be the major sub-set of T lymphocytes in the HPV positive laryngeal squamous cell carcinoma microenvironment. Background: To examine the prognostic significance of human papillomavirus (HPV) status in relation to the ratio of CD4/CD8 in LSCC. Methods: In this study, 46 LSCC biopsy samples were retrospectively assessed using immunohistochemistry for CD4+ and CD8+ tumor infiltrating lymphocytes (TILs). HPV status was determined by HPV in situ hybridization (ISH) and p16INK4A immunohistochemistry. Of the 46 samples, 21 were evaluated for the expression of IFN-γ and IL-4 by quantitative real-time PCR (qRT-PCR). The influence of HPV status on locoregional tumor control and T-cell sub-sets infiltrating tumor microenvironment were investigated. Results: Nineteen patients (41.3%) were classified as HPV positive, who had improved disease-free survival (28% in reduction, hazard ratio =0.10; 95% CI =0.011–0.938). A direct correlation between the HPV status and the ratio of CD4/CD8 or mean levels of CD8+ T cells was observed. Compared with the HPV-negative samples, HPV-positive samples had a higher ratio of IFN-γ/IL-4 (24.43 ± 29.89 vs 3.90 ± 4.03; p = 0.0375).

Extended pelvic resections for the treatment of locally advanced and recurrent anal canal and colorectal cancer: technical aspects and morbimortality predictors aftet 24 consecutive cases.

to evaluate the profile of morbidity and mortality and its predictors related to extensive pelvic resections, including pelvic exenteration, to optimize the selection of patients and achieve better surgical results. we performed 24 major resections for anorectal pelvic malignancy from 2008 to 2015 in the Instituto do Câncer do Ceará. The factors analyzed included age, weight loss, resected organs, total versus posterior exenteration, angiolymphatic and perineural invasion, lymph node metastasis and overall and disease-free survival. the median age was 57 years and the mean follow-up was ten months. Overall morbidity was 45.8%, with five (20.8%) serious complications. There were no deaths in the first 30 postoperative days. The median overall survival was 39.5 months, and disease-free survival, 30.7 months. Concomitant resection of the bladder was an isolated prognostic factor for higher risk of complications (87.5% vs. 26.7%, p = 0.009). Angiolymphatic invasion and lymph node metastasis did not reach significance with respect to disease-free survival. treatment of advanced anorectal tumors is challenging, often requiring combined resections, such as cystectomy and sacrectomy, and complex reconstructions. The magnitude of the operation still carries a high morbidity rate, but is a procedure considered safe and feasible, with a low mortality and adequate locoregional tumor control when performed in referral centers. avaliar o perfil de morbimortalidade e seus fatores preditivos relacionados às ressecções pélvicas extensas, incluindo a exenteração pélvica, com o intuito de otimizar a seleção dos pacientes e obtenção de melhores resultados cirúrgicos. foram realizadas 24 grandes ressecções pélvicas por neoplasia maligna anorretal de 2008 a 2015 no Instituto do Câncer do Ceará. Os fatores analisados incluíram idade, perda de peso, órgão ressecados, exenteração total versus posterior, invasão angiolinfática e perineural, metástase linfonodal e sobrevida global e livre de doença. a mediana de idade foi 57 anos e o tempo médio de seguimento foi dez meses. A morbidade global foi 45,8%, com cinco (20,8%) complicações graves. Não houve óbito nos primeiros 30 dias de pós-operatório. A sobrevida global média foi 39,5 meses e a sobrevida livre de doença foi 30,7 meses. A ressecção concomitante da bexiga foi fator prognóstico isolado com maior risco para complicações (87,5% vs. 26,7%, p=0.009). Invasão angiolinfática e metástase linfonodal não alcançaram significância com relação à sobrevida livre de doença. o tratamento dos tumores anorretais avançados é desafiador, necessitando frequentemente de ressecções combinadas, como a cistectomia e sacrectomia, além de reconstruções complexas. A magnitude da cirurgia ainda carrega uma elevada taxa de morbidade, porém é um procedimento considerado seguro e factível, com uma baixa mortalidade e adequado controle locorregional tumoral quando realizado em centros de referência.

Personalized Radiation Oncology: Epidermal Growth Factor Receptor and Other Receptor Tyrosine Kinase Inhibitors.

Molecular biomarkers are currently evaluated in preclinical and clinical studies in order to establish predictors for treatment decisions in radiation oncology. The receptor tyrosine kinases (RTK) are described in the following text. Among them, the most data are available for the epidermal growth factor receptor (EGFR) thatplays a major role for prognosis of patients after radiotherapy, but seems also to be involved in mechanisms of radioresistance, specifically in repopulation of tumour cells between radiotherapy fractions. Monoclonal antibodies against the EGFR improve locoregional tumour control and survival when applied during radiotherapy, however, the effects are heterogeneous and biomarkers for patient selectionare warranted.Also other RTK´ssuch as c-Met and IGF-1R seem to playimportant roles in tumour radioresistance.Beside the potential to select patients for molecular targeting approaches combined with radiotherapy,studies are also needed to evluate radiotherapy adaptation approaches for selected patients, i.e. adaptation of radiation dose, or, more sophisticated, of target volumes.

Indications for Salivary Gland Radiotherapy.

There is an established role for post-operative radiotherapy in the treatment of benign and malignant salivary gland tumours. For benign disease, the addition of radiotherapy improves local tumour control in cases with incomplete excision, involved surgical margins or multi-focal disease recurrence. After capsule rupture or spillage alone, surveillance should usually be advised. For malignant disease, post-operative radiotherapy is recommended for an advanced tumour stage, high-grade tumour, perineural or lympho-vascular invasion, close or positive resection margins, extra-parotid extension or lymph node involvement. The main benefit is increased loco-regional tumour control, although this may translate into a modest improvement in survival. The possible late side effects of parotid bed irradiation include skin changes, chronic otitis externa, sensorineural hearing loss, osteoradionecrosis and secondary malignancy. Severe complications are rare, but patients should be counselled carefully about the risks. Primary radiotherapy is unlikely to be curative and is reserved to cases in which resection would cause unacceptable functional or cosmetic morbidity or would likely result in subtotal resection (R2) or to patients with distant metastases to gain local tumour control. There are provisional data on the use of charged particle radiotherapy in this setting. Some patients may benefit from synchronous chemotherapy with radiotherapy, but this group is not defined, and data from comparative prospective studies are required before routine clinical use of this treatment.

Place du curage ganglionnaire avant radiothérapie exclusive dans la prise en charge des carcinomes épidermoïdes localement évolués des voies aérodigestives supérieures

PurposeOptimal timing of neck dissection remains debated in the conservative management of patients with locoregionally advanced squamous cell carcinoma of the head and neck. Patients and methodsThe files of 63 patients with radiographic evidence of bulky or necrotic nodal metastases treated by up-front neck dissection and definitive radiotherapy between 2000 and 2012 at two institutions were retrospectively reviewed. ResultsThe primary site was oropharyngeal, hypopharyngeal or laryngeal in 63%, 21% and 13% cases, respectively. Overall, 83% of the tumours were staged pN2b or more. Extracapsular spread was found in 48 cases (77%). After a 48-month median follow-up, the 3-year locoregional control and overall survival were 88% and 68%, respectively. Only one isolated failure occurred in the dissected neck. ConclusionThis combination therapy provides a good locoregional tumour control. It should be considered as an option in laryngeal, hypopharyngeal or oropharyngeal squamous cell carcinomas with bulky or necrotic nodal metastases at presentation.

Embryologically based radical hysterectomy as peritoneal mesometrial resection (PMMR) with pelvic and para-aortic lymphadenectomy for loco-regional tumor control in endometrial cancer: first evidence for efficacy

ObjectiveTo evaluate the feasibility and efficacy of embryologically based compartmental surgery for locoregional tumor control in intermediate and high risk endometrial cancer: peritoneal mesometrial resection with therapeutic pelvic and para-aortic lymphadenectomy by robotically assisted laparoscopy.Methods75 consecutive surgically treated patients with uterine malignancies have been analyzed. 68 patients with histologically proven endometrial cancer and complete robotically assisted surgery have been included in this study on morbidity and oncological outcome. 56 % of the patients were at intermediate/high risk with either stage IAG3 or IB (n = 22) or stage II–IV (n = 16). Adjuvant EBRT was offered to three patients only (4 %), whereas five received isolated vaginal brachytherapy (7 %). Indocyanine-green (ICG) fluorescence lymphography is demonstrated being useful for additional intraoperative visualization of the compartment borders and lymphatic drainage to the postponed lymph compartments.ResultsAfter a mean follow-up of 32 months, there were only two loco-regional recurrences (2.9 %). Both recurrences were apparently cured by salvage therapy. 9 patients died; 6 (8.8 %) from metastatic disease (5) or unknown cause (1), 3 (4.4 %) from intercurrent disease without evidence of disease. One patient (1.4 %) experienced a peritoneal carcinosis and is alive. There were 8/68 perioperative complications (12 %). No perioperative mortality was observed.ConclusionsEmbryologically defined compartmental surgery by robotically assisted laparoscopy seems to be feasible and safe in endometrial cancer. The low loco-regional recurrence rate of 2.9 % in spite of a very low percentage of adjuvant radiotherapy and 56 % of intermediate/high risk tumors should stimulate to initiate a multicentre trial to evaluate the value of compartmental surgery for prevention of locoregional recurrence in endometrial cancer.