Favorable safety profile of moderate hypofractionated over normofractionated radiotherapy in breast cancer patients: a multicentric prospective real-life data farming analysis.

BACKGROUND: Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe and efficient as normofractionated radiotherapy (NFRT) in randomized trials resulting in major changes in clinical practice. Toxicity rates observed in selected clinical trial patients may differ from those observed in unselected patients with possible comorbidities and frailty in real-life. This study aimed to examine the influence of HFRT versus NFRT on acute toxicity and identify risks factors of dermatitis in real-life patients. MATERIALS AND METHODS: Prospective data from breast cancer patients, treated with locoregional radiotherapy were collected between November 2015 and February 2020 in 3 comprehensive cancer centers. Through a systematic data-farming strategy, acute toxicity evaluation forms (CTCAEv4.0) were prospectively completed and extracted electronically. The results from each center were then anonymously merged into a single database for analysis. A Chi-2 test was used to compare HFRT and NFRT. Furthermore, risk factors of dermatitis were identified in a sub-study (622 patients) by multivariate logistic regression analysis. RESULTS: In total, 3518 T0-4 N0-3 mostly M0 (85.8%) breast cancer patients with a median age of 60.7 (24-96 years old) were analyzed. Acute grade 2-3 dermatitis, grade 1-3 breast oedema, and grade 1-2 hyperpigmentation were less frequent with HFRT versus NFRT: respectively 8.9% versus 35.1% (Chi-2 = 373.7; p < 0.001), 29.0% versus 37.0% (Chi-2 = 23.1; p < 0.001) and 27.0% versus 55.8% (Chi-2 = 279.2; p < 0.001). Fewer patients experienced pain with HFRT versus NFRT: 33.4% versus 53.7% respectively (Chi-2 = 137.1; p < 0.001). Factors such as high BMI (OR = 2.30 [95% CI, 1.28-4.26], p < 0.01), large breast size (OR = 1.88 [95% CI, 1.07-3.28], p < 0.01) and lumpectomy over mastectomy (OR = 0.52 [95% CI, 0.27-0.97], p < 0.05) were associated with greater risk factors of grade 2-3 dermatitis in multivariate analysis regardless of NFRT or HFRT. CONCLUSION: The results of this study suggests that breast HFRT may be a better option even for patients with a high BMI or large breast size. Acute toxicity was low to mild, and lower with HFRT compared to NFRT. Results from real-life data were robust, and support the use of HFRT beyond randomized study populations. Long-term real-life data awaits further investigation.

Prognostic Factors and Survival Score for Patients With Anaplastic Thyroid Carcinoma: A Retrospective Study from a Regional Registry.

BACKGROUND/AIM: Anaplastic thyroid carcinoma (ATC) is the least common but most lethal of thyroid cancer, despite various therapeutic options, with limited efficacy. In order to help therapeutic decision-making, the purpose of this study was to develop a new prognostic score providing survival estimates in patients with ATC. PATIENTS AND METHODS: Based on a multivariate analysis of 149 retrospectively analyzed patients diagnosed with ATC from 1968 to 2017 at a referral center, a propensity score was developed. A model was generated providing survival probability at 6 months and median overall survival estimates. RESULTS: The median survival was 96 days. The overall survival rate was 35% at 6 months, 20% at 1 year and 13% at 2 years. Stepwise Cox regression revealed that the most appropriate death prediction model included metastatic spread, tumor size and age class as explanatory variables. This model made it possible to define three categories of patients with different survival profiles. CONCLUSION: Distant metastasis, age and primary tumor size are strong independent factors that affect prognosis in patients with ATC. Using these significant pretreatment factors, we developed a score to predict survival in these patients with poor prognosis.

Primary gastric synovial sarcoma: A case report and literature review.

INTRODUCTION: Synovial sarcoma (SS) is a mesenchymal neoplasm that is characterized by its unique histological pattern and is most commonly found near the joints of the extremity. Stomach involvement is very rare. This work aimed to present the case of a patient with gastric SS. We also conducted a review of 39 gastric SS cases reported in the literature. PRESENTATION OF CASE: Here we report a case of primary gastric synovial sarcoma in a 32-year-old male patient revealed by gastric reflux. Partial gastrectomy was performed showing a 35 mm lesion with a high spindle cell component. Immunohistochemistry revealed 18q11.2 translocation expression in most of the cells asserting a diagnosis of SS. No local or distant recurrence occurred at 8 months post-operative follow-up. DISCUSSION: The majority of SS occurs in the extremities and is most often associated with tendons in the large articulations of young adults. Gastric SS are very scarce and a molecular biology approach to detect the SYT-SSX fusion gene is required for conclusive diagnosis. We carried out a clinical review of the 40 cases of primary gastric SS, including our case. They all underwent an excisional surgery, most of them by partial gastectomy or wedge resection. Recurrences were rare and early when they occurred. CONCLUSION: Gastric SS is a very uncommon neoplasia although it is henceforth a described entity. Immunohistochemical detection of a pathognomonic translocation is needed to make the diagnosis of SS. Best therapeutic approach for these tumors remains surgical resection with no specific excisional technique recommended.

18F-FDG PET/CT in Oral Cuniculatum Carcinoma.

A 69-year-old woman was referred for initial staging of an oral cavity mass. F-FDG PET/CT displayed a homogeneous intense uptake of the 50-mm left hemipalatal mass with local extension to the dental arcade and maxillary sinus. Infracentimetric bilateral cervical nodes with faint uptake were also detected, contrasting with the usual presentation of other head and neck squamous cell carcinoma. Biopsy concluded to a rare head and neck squamous cell carcinoma subtype: oral cuniculatum carcinoma (OCC). After radiotherapy, 18F-FDG PET/CT showed metabolic complete response. Our case describing specifically the metabolic characteristics of OCC and radiotherapy evaluation for this rare tumor.

Prognostic factors in patients with soft palate squamous cell carcinoma.

BACKGROUND: To define the prognostic factors associated with outcome in patients with soft palate squamous cell carcinoma (SCC). METHODS: Previously untreated patients with soft palate and uvula SCC treated in our institution between 1997 and 2012 were collected. The prognostic value of clinical, hematological, and treatment characteristics was examined. RESULTS: We identified 156 patients, median age 58 years, with 71% drinkers, 91% smokers; 19% had synchronous cancer. Front-line treatment was chemoradiotherapy in 58 (37%), radiotherapy alone in 60 (39%), surgery in 17 (11%), and induction chemotherapy in 21 patients (14%). The 5-year actuarial overall survival (OS) and progression-free survival (PFS) were 41% and 37%, respectively. In univariate analysis, T3-T4 vs T1-T2 stage, N2-N3 vs N0-N1 stage, and neutrophil count >7 g/L were associated with worse OS and PFS (P < .05). CONCLUSION: In patients with soft palate SCC, inflammation biomarkers were associated with OS.

Is dose de-escalation possible in sarcoma patients treated with enlarged limb sparing resection?

PURPOSE: To evaluate the impact of dose de-escalation in a large series of resected limbs soft tissue sarcomas (STS). METHODS: Data were retrospectively analysed from 414 consecutive patients treated for limb STS by enlarged surgery and radiotherapy at Gustave Roussy from 05/1993 to 05/2012. Radiotherapy (RT) dose level was decided by the multidisciplinary staff and depended upon the quality of surgery and margins size. RESULTS: RT was delivered prior (13%) or after (87%) surgery. Seven patients (2%) had pre- and a postoperative RT boost. Median delivered RT dose was 50 Gy (36-70 Gy), and 33% received ≥55 Gy. At a median follow-up of 6.8 years, the 5-year actuarial local relapse (LR) rate was 7% (95% CI: 4.4-10%). The median time to the first LR was 2.7 years (range: 0.6-11.2 years). The LR was most often located within the irradiated field (26/32; 81%), where the median total applied dose was 56 Gy (range, 40-60 Gy). The 5-year LR rates were 4%, and 15% in patients receiving <55 Gy, and in those who had ≥55 Gy (p < 0.001), respectively. In the multivariate analysis, dose ≥55 Gy (HR [hazard ratio]: 2.9; p = 0.02), certain histological subtypes (HR: 7.8; p < 0.001), and minimal surgical margins <1 mm (HR: 2.9; p = 0.02) were associated to higher LR rates. In the subgroup of patients with "positive" margins <1 mm (n = 102), these histological subtypes (HR: 4.4; p = 0.03), and inadequate initial surgery justifying re-excision (HR: 3; p = 0.048) predicted for an increased LR, whereas dose of irradiation did not (p = 0.2). Patients who had late complications (n = 64; 15%) received higher doses of irradiation as compared with other patients (median: 55 Gy vs. 50 Gy, respectively; p < 0.001). CONCLUSION: In this retrospective analysis of patients having enlarged surgery and RT, histological subtype is the strongest predictor of LR, whereas dose de-escalation did not lead to worse outcomes. A dose of 50 Gy may be recommended in case of planned enlarged surgery with R0 margins.

Hypofractionated Regional Nodal Irradiation for Women With Node-Positive Breast Cancer.

PURPOSE: To evaluate the effect of hypofractionated radiation therapy (HFRT) of the breast/chest wall and regional nodes on overall survival (OS), disease-free survival (DFS), locoregional control and on treatment-related toxicity in patients with breast cancer and nodal involvement. METHODS AND MATERIALS: Two hundred fifty-seven patients treated between October 2009 and June 2011 with hypofractionated locoregional radiation therapy (42 Gy in 15 fractions) were retrospectively reviewed, 51 (19.8%) after breast-conserving surgery and 206 (80.2%) after radical surgery. Patients treated with breast-conserving surgery received a boost dose to the tumor bed (delivered by photons, electrons, or interstitial high-dose-rate brachytherapy). Two hundred fifty-six (99.6%) patients underwent chemotherapy, 209 (81.3%) had hormonal treatment, and 65 (25.3%) had anti-HER2 targeted therapy. RESULTS: The median follow-up time was 64 months (range, 11-88 months). The rates of 5-year OS, DFS, locoregional recurrence (LRR)-free survival, and distant metastasis (DM)-free survival were 86.6%, 84.4%, 93.9%, and 83.1%, respectively. In multivariate analysis (MVA), lymph node ratio >65%, lymphovascular invasion, and negative hormone receptor status predicted for OS, DSF, and DM. T3 to 4 stage was also associated with worse DFS and DM. Finally, for LRR the independent prognostic factors on MVA were N2 to 3 stage and grade 3. Hyperpigmentation was observed in 19.2% of patients, telangiectasia in 12.3%, and fibrosis in 30.7%. Grade ≥2 lymphedema was recorded in 5.8% of cases. During the study follow-up, no cardiac or symptomatic pneumonitis was observed, nor were plexopathy or rib fractures. CONCLUSION: According to the findings from this retrospective study, HFRT seems to be an acceptable alternative for patients with breast cancer who need regional nodal irradiation. However, prospective randomized trials are necessary to confirm these preliminary results.

Primary Extremity Soft Tissue Sarcomas: Does Local Control Impact Survival?

BACKGROUND: The objective of this study was to evaluate the adequate margin in the local treatment of extremity soft tissue sarcomas (ESTS) and understand the relationship between local control and overall survival (OS). METHODS: All consecutive patients treated for a primary ESTS at a single center from 1993 to 2012 were reviewed. RESULTS: In all, 531 patients were included. Twelve (2 %) underwent a first-line amputation. The resections were R0/R1/not available in 434 (82 %), 92 (17 %), and 5 patients (1 %). The median tumor size was 8 cm, and the tumor grades were 1 (n = 132), 2 (n = 201), and 3 (n = 195). The median size of the minimal margin was 2 mm on fixed specimen. Preop or postop chemotherapy was administered to 222 patients, and 414 received radiotherapy. With a median follow-up period of 7 years, the 5-year actuarial local recurrence (LR) rate and OS were 8 % (95 % CI, 6-11 %) and 80 % (95 % CI, 76-83 %). Predictors of worse OS were grade 3, leiomyosarcoma, male gender, and age >60 years, whereas tumor size, margin status, and LR were not. Among patients requiring re-excision (n = 252), the presence of residual cells correlated with OS but not LR. After preoperative treatment, a percentage of residual cells ≥10 % correlated with OS but not LR. In the multivariate analysis, specific subtypes (epithelioid sarcoma and myxofibrosarcoma) and margin size <1 mm correlated with LR, whereas grade and the tissue constituting the surgical margins did not. CONCLUSIONS: Specific subtypes and surgical margin size <1 mm were correlated with a higher LR. Neither the margin status nor LR affect OS.

[Radiotherapy for endometrial cancer: experience of the national institute of oncology with 52 cases]. / La radiothérapie du cancer de l'endomètre: expérience de l'institut national d'oncologie à propos de 52 cas.

Endometrial cancer is the most common gynecological cancer in the Western world. It affects mainly postmenopausal women. The aim of our study is to report the experience of the radiotherapy department of the National Oncology Institute (INO) in the treatment of endometrial cancer. We retrospectively analyzed 52 cases of endometrial cancer treated in the INO radiotherapy department between 2007-2009. Data obtained from the patient medical records were related to the epidemiologic, clinical, therapeutic and evolutionary aspects of this cancer. The median age of the patients was 57 years, 87% were postmenopausal. The median of consultation time was six months. The main symptom was metrorrhagia (51 patients). Histological diagnosis was based on biopsic curettage of uterine endometrium in 51% of the cases. Anatomo-pathological examination showed an endometrioid adenocarcinoma in 92% of the cases. After the assessment, 27% of the patients were stage I, 30% stage II, 20% stage III and 1% stage IVA, according to the International Federation of Gynecological and Obstetrics (FIGO) stage classification. After surgery, 51% of the patients received postoperative external radiotherapy. The delivered dose was 46 Gray (Gy). All patients received internal vaginal brachytherapy. From an evolutionary perspective, 83% of the patients had no recurrences during the follow-up period, 8% of patients had a local recurrence and 4% of patients had distant metastases. Therefore, surgery is the main treatment for endometrial cancer. Radiotherapy is the primary adjuvant treatment.

Toxicity of concomitant cetuximab and radiotherapy with or without initial taxane-based induction chemotherapy in locally advanced head and neck cancer.

BACKGROUND: The purpose of this study was to evaluate the tolerability of concurrent radiotherapy and cetuximab (bioradiotherapy [BRT]) after taxane-based induction chemotherapy in head and neck squamous cell carcinoma (HNSCC). METHODS: One hundred four patients with HNSCC received BRT with (29%) or without (71%) prior taxane-based induction chemotherapy. RESULTS: Radiodermatitis (97%) and skin rash (65%) occurred frequently, but there was no difference of occurrence or the grade of the rash observed in the 2 populations. However, patients receiving taxane-based induction chemotherapy had a less severe rash as compared with patients without induction chemotherapy. Mucositis and dysphagia were frequent and comparable in the 2 groups. The occurrence of a skin rash (at any grade) did not predict an increased overall survival (OS) in the overall population, but it was associated with an improved 3-year OS in patients receiving taxane-based induction chemotherapy. OS was not influenced by the skin rash grade in the overall population of the 2 treatment subgroups. CONCLUSION: Taxane-based induction chemotherapy did not increase the rate of cetuximab-related toxicities. © 2015 Wiley Periodicals, Inc. Head Neck 38: E905-E910, 2016.

Feasibility of radiotherapy or chemoradiotherapy after taxane-based induction chemotherapy for nonoperated locally advanced head and neck squamous cell carcinomas.

To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.

Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas.

AIM: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73%) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27%) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). RESULTS: Median follow-up was 29 months. In all, 56% of patients treated with CRT received the planned three cycles (92% at least two cycles) and 79% patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72% and 61%, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79%, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76% for CRT vs. 61% for BRT) and DC (2-year LRC: 81% for CRT vs. 68% for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). CONCLUSION: This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.