Brain radiotherapy in patients treated for a newly diagnosed primary central nervous system lymphoma: professional practice evaluation in 19 French centers.

INTRODUCTION: The objective of this study was a multicentric evaluation of professional practices, analyzing the irradiation technique itself and its impact on survival and recurrence sites, in primary central nervous system lymphomas (PCNSLs). METHODS: We retrospectively analyzed the technical and clinical records of 79 PCNSL patients included in the database of the national expert network for oculocerebral lymphoma ('LOC') who were treated with brain radiotherapy as first-line treatment for newly diagnosed primary central nervous system lymphoma between 2011 and 2018. RESULTS: The number of patients treated with brain radiotherapy gradually decreased over time. The heterogeneity of radiotherapy prescriptions was significant, and 55% of them did not comply with published recommendations in terms of irradiation dose and/or volume. The proportion of complete responders to induction chemotherapy treated with reduced-dose radiotherapy increased over time. Partial brain radiotherapy was associated with significantly lower overall survival in univariate analysis. In partial responders to induction chemotherapy, increasing the total dose to the brain >30 Gy and adding a boost to the WBRT induced a trend toward improved progression-free and overall survival. Five recurrences (13%) occurred exclusively in the eyes, all in patients whose eyes had been excluded from the irradiation target volume and including 2 patients without ocular involvement at diagnosis. CONCLUSION: The visibility of recommendations for prescribing brain radiotherapy for the treatment of newly diagnosed primary central nervous system lymphoma needs to be improved to harmonize practices and improve their quality. We propose an update of the recommendations.

Prognostic Impact of Pretherapeutic FDG-PET in Localized Anal Cancer.

Due to the heterogeneity of tumour mass segmentation methods and lack of consensus, our study evaluated the prognostic value of pretherapeutic positron emission tomography with fluorodeoxyglucose (FDG-PET) metabolic parameters using different segmentation methods in patients with localized anal squamous cell carcinoma (SCC). Eighty-one patients with FDG-PET before radiochemotherapy were retrospectively analyzed. Semiquantitative data were measured with three fixed thresholds (35%, 41% and 50% of Maximum Standardized Uptake Value (SUVmax)) and four segmentation methods based on iterative approaches (Black, Adaptive, Nestle and Fitting). Metabolic volumes of primary anal tumour (P-MTV) and total tumour load (T-MTV: P-MTV+ lymph node MTV) were calculated. The primary endpoint was event-free survival (EFS). Seven multivariate models were created to compare FDG-PET tumour volumes prognostic impact. For all segmentation thresholds, PET metabolic volume parameters were independent prognostic factor and T-MTV variable was consistently better associated with EFS than P-MTV. Patient's sex was an independent variable and significantly correlated with EFS. With fixed threshold segmentation methods, 35% of SUVmax threshold seemed better correlated with EFS and the best cut-off for discrimination between a low and high risk of event occurrence was 40 cm3. Determination of T-MTV by FDG-PET using fixed threshold segmentation is useful for predicting EFS for primary anal SCC. If these data are confirmed in larger studies, FDG-PET could contribute to individualized patient therapies.

High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study.

INTRODUCTION: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. PATIENTS AND METHODS: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis (NCT01219790). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. RESULTS: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). CONCLUSION: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.

Safety and outcome of chemoradiotherapy in elderly patients with rectal cancer: results from two French tertiary centres.

BACKGROUND: The risks of chemoradiotherapy in elderly patients with rectal cancer have not yet been well-characterised. METHODS: We retrospectively reviewed the charts of patients with rectal cancer over 70 years old who were treated with chemoradiotherapy in two French university hospitals. RESULTS: A total of 125 patients were evaluated. Mean age was 75.1 ± 4.1 years and ranged from 70 to 90 years. Adverse effects ≥ grade 2 were observed in 32% of the patients and adverse effects ≥ grade 3 in 15%. Dose reduction for toxicity was performed in 18% of the patients and chemoradiotherapy discontinuation was necessary in 9%. Postoperative morbidity was 16% with two treatment-related deaths. Two-year survival rate was 84%. No variables had any influence on treatment-related adverse events. CONCLUSIONS: In selected elderly patients, chemoradiotherapy is well-tolerated, without any significant increase in adverse events, and the results are similar to those recorded in younger patients.

Esophageal cancer in the elderly: an analysis of the factors associated with treatment decisions and outcomes.

BACKGROUND: Only limited data has been reported so far regarding oesophageal cancer (EC) in elderly patients. The aim of the study is to identify the baseline parameters that influenced therapeutic decision. METHODS: All consecutive patients 70 years or older being treated for EC were retrospectively analyzed. Patients without visceral metastasis were divided into two groups: treatment with curative intent (chemoradiotherapy, surgery, radiotherapy, mucosectomy or photodynamic therapy) or best supportive care (BSC). Patients with metastasis were divided into two groups: palliative treatment (chemotherapy, chemoradiotherapy or radiotherapy) or BSC. RESULTS: Two hundred and eighty-two patients were studied. Mean age was 76.5 ± 5.5 years and 22.4% of patients had visceral metastasis. In patients without visceral metastasis (n = 220) the majority had treatment with curative intent (n = 151) whereas in patients with metastasis (n = 62) the majority had BSC (n = 32). Severe adverse events (≥ grade 3) were observed in only 17% of the patients. Patients without specific carcinologic treatment were older, had more weight loss, worse WHO performance status and Charlson score in multivariate analysis. DISCUSSION: Our results suggest that elderly patients with an EC could benefit from cancer treatment without major toxicities. Weight loss, WHO performance status and the Charlson score could be used to select the appropriate treatment in an elderly patient.

Baseline nutritional status is predictive of response to treatment and survival in patients treated by definitive chemoradiotherapy for a locally advanced esophageal cancer.

OBJECTIVES: To assess the impact of baseline nutritional status on treatment response and survival in nonmetastatic patients with a locally advanced esophageal cancer (LAEC) treated with definitive chemoradiotherapy (CRT). METHODS: One hundred five patients with LAEC treated by definitive CRT were retrospectively included. The CRT regimen was based on an external radiotherapy (RT) delivered concomitantly to a cisplatin-based chemotherapy (CT). Patients were considered to have a complete response (CR) to CRT when no residual tumor was detected on CT scan and esophagoscopy performed 2 months after the end of CRT. Multivariate analysis of predictive factors of response to CRT and survival were performed using a logistic regression and a Cox model, respectively. RESULTS: Mean value of baseline nutritional parameters was significantly different between nonresponder (N = 42) and responder (N = 63) patients to CRT (weight loss 10%vs 5.8%, P= 0.0047; serum albumin level 35 g/L vs 38.7 g/L, P= 0.0004; BMI 22.8 kg/m2vs 25.2 kg/m2, P= 0.01). In multivariate analysis, serum albumin level > 35 g/L was the only independent predictive factor of CR to CRT (P= 0.009). Independent prognostic factors of survival were BMI > 18 kg/m2 (P= 0.003), dysphagia Atkinson score <2 (P= 0.008), dose of RT > 50 Grays (Gy) (P < 0.0001) and CR to CRT (P < 0.0001). CONCLUSIONS: Survival was influenced by baseline nutritional status as well as dysphagia, dose of RT, and CR to CRT. Despite the retrospective design of the study, our results may provide the concept basis for performing a prospective nutritional intervention study in patients treated by definitive CRT for an esophageal cancer.

Response to definitive chemoradiotherapy and survival in patients with an oesophageal adenocarcinoma versus squamous cell carcinoma: a matched-pair analysis.

OBJECTIVES: The impact of the histological tumour type in patients treated with definitive chemoradiotherapy (CRT) for an oesophageal cancer is not well established. The aim of this retrospective matched-pair analysis was to evaluate the clinical complete response (CCR) to definitive CRT and the outcome between 2 groups of patients. METHODS: Fifty-seven patients with an oesophageal adenocarcinoma (ADC) were matched according to the tumour stage and the WHO performance as well as the CRT regimen status including 57 patients with an oesophageal squamous cell carcinoma (SCC). CRT was based on radiotherapy combined with a cisplatin-based chemotherapy. RESULTS: A CCR was observed in 40 patients (70.2%) with an SCC as compared with 26 patients (45.6%) with an ADC (p = 0.013). SCC patients received significantly more of planned cisplatin and radiotherapy doses than ADC patients (82.0 vs. 67.7%, p = 0.042, and 92.5 vs. 84.5%, p = 0.023, respectively). In responders to CRT, local recurrence was significantly more frequent in SCC patients (52.5 vs. 26.9%, p = 0.046). Median survival in all patients as well as in responders to CRT was not different between the 2 groups. CONCLUSION: Our study showed that treatment completion and CCR to definitive CRT were more frequent in SCC with, however, more local recurrences in these patients. Further studies are required to confirm this difference in response rate to definitive CRT according to histological type of the tumour in oesophageal cancer.

Impact of radiation schedule and chemotherapy duration in definitive chemoradiotherapy regimen for esophageal cancer.

UNLABELLED: Impact of radiotherapy (RT) schedule on local response and duration of the 5-fluorouracil/cisplatin (5 FU/CDDP) chemotherapy (CT) on m are still questioning in chemoradiotherapy (CRT) regimen in esophageal carcinoma. AIM: Evaluate two RT schedules and two different CT durations by a retrospective comparison of the CRT regimens used by two centres between 1994 and 2000. METHODS: In centre I (regimen I), patients received 2 CT concomitantly to a continuous RT (50 Gy/25 fractions/5 weeks). In centre II (regimen II), patients received 6 CT, 3 were concomitant to a split course RT (20 Gy/10 fractions x 3 courses) and 3 CT were delivered after CRT. RESULTS: A total of 129 patients were included, 74 in centre I and 55 in centre II respectively. Main patient characteristics were similar between the two groups. Clinical complete response to CRT was significantly more frequent in regimen I (83.8% vs 65.4%; P=0.02). The median overall survival (OS) was 20 months in regimen I and 22 months in regimen II (NS). During follow-up, responder patients to CRT in regimen II experienced significant fewer metastasis (51.6% vs 27.8%; P=0.03) with a trend to an increased 5-year survival (19.4% vs 11.3%) and OS (26.5 vs 21.0 months) (NS). Grade 3-4 toxicities were not different. CONCLUSION: Clinical complete response to CRT was significantly more frequent with a continuous RT whereas additional CT after CRT significantly reduced metastasis occurrence. CRT regimen in esophageal carcinoma may be more effective using a continuous RT schedule and additional CT courses after CRT completion.