A Quality Control Study on Involved Node Radiation Therapy in the European Organisation for Research and Treatment of Cancer/Lymphoma Study Association/Fondazione Italiana Linfomi H10 Trial on Stages I and II Hodgkin Lymphoma: Lessons Learned.

PURPOSE: Involved node radiation therapy (INRT) was introduced in the European Organisation for Research and Treatment of Cancer/Lymphoma Study Association/Fondazione Italiana Linfomi H10 trial, a large multicenter trial in early-stage Hodgkin Lymphoma. The present study aimed to evaluate the quality of INRT in this trial. METHODS AND MATERIALS: A retrospective, descriptive study was initiated to evaluate INRT in a representative sample encompassing approximately 10% of all irradiated patients in the H10 trial. Sampling was stratified by academic group, year of treatment, size of the treatment center, and treatment arm, and it was done proportional to the size of the strata. The sample was completed for all patients with known recurrences to enable future research on relapse patterns. Radiation therapy principle, target volume delineation and coverage, and applied technique and dose were evaluated using the EORTC Radiation Therapy Quality Assurance platform. Each case was reviewed by 2 reviewers and, in case of disagreement also by an adjudicator for a consensus evaluation. RESULTS: Data were retrieved for 66 of 1294 irradiated patients (5.1%). Data collection and analysis were hampered more than anticipated by changes in archiving of diagnostic imaging and treatment planning systems during the running period of the trial. A review could be performed on 61 patients. The INRT principle was applied in 86.6%. Overall, 88.5% of cases were treated according to protocol. Unacceptable variations were predominately due to geographic misses of the target volume delineations. The rate of unacceptable variations decreased during trial recruitment. CONCLUSIONS: The principle of INRT was applied in most of the reviewed patients. Almost 90% of the evaluated patients were treated according to the protocol. The present results should, however, be interpreted with caution because the number of patients evaluated was limited. Individual case reviews should be done in a prospective fashion in future trials. Radiation therapy Quality Assurance tailored to the clinical trial objectives is strongly recommended.

Outcomes in N3 Head and Neck Squamous Cell Carcinoma and Role of Upfront Neck Dissection.

OBJECTIVES: We investigated the prognostic factor of N3 head and neck squamous cell carcinoma (HNSCC), including the role of upfront neck dissection (UFND) before radiotherapy (RT). METHODS: We retrospectively reviewed the charts of consecutive N3 HNSCC patients treated with curative intent RT. RESULTS: In the study, 323 N3 HNSCC patients were included. Of those, 125 patients (39%) had UFND. Median follow-up was 3.9 years (0-14.8 years). Overall survival (OS) at 5 years was 31.2%, and progression-free survival (PFS) was 26%. In the multivariate analysis, OS was improved in PS 0, T1-2 tumors, patients receiving concurrent chemotherapy, never or former smokers, and UFND. UFND was strongly associated with increased OS (45.7% vs. 21.2%, P < .001), and PFS (P < .001). Regardless of neck node size, UFND improved survival (P = .001 for ≤ 7 cm and P = .004 for > 7 cm). CONCLUSION: UFND could improve treatment outcomes in N3 HNSCC, especially for non-oropharyngeal cancer, regardless of neck node size. LEVEL OF EVIDENCE: 2B Laryngoscope, 131:E844-E850, 2021.

Radiation Therapy Department Reorganization during the Coronavirus Disease 2019 (COVID-19) Outbreak: Keys to Securing Staff and Patients During the First Weeks of the Crisis and Impact on Radiation Therapy Practice from a Single Institution Experience.

PURPOSE: During the first weeks of the coronavirus disease 2019 (COVID-19) outbreak in France, it was necessary to clearly define organizational priorities in the radiation therapy (RT) departments. In this report, we focus on the urgent measures taken to reduce risk for both our staff and patients by reducing the number of patients receiving treatment. METHODS AND MATERIALS: We reviewed the fractionation schemes for all patients in our department, including those receiving treatment and those soon to start treatment. Our goals were to (1) decrease the number of patients coming daily to the hospital for RT, (2) adapt our human resources to continue patients' care in the department, and (3) help to cover understaffed COVID-19 sectors of the hospital. RESULTS: We identified 50 patients who were receiving treatment (n = 6), were going to start radiation after CT scan simulation (n = 41), or for whom the CT scan was pending (n = 3). The majority were women (64%) treated for breast cancer (54%). RT was delayed for 22 (44%) patients. The majority were offered hormone therapy as "waiting therapy." Hypofractionation was considered in 21 (42%) patients mainly with breast cancer (18 of 21, 86%). The number of courses initially planned and replanned as a result of the COVID-19 outbreak during the period of March 15 to May 31, 2020, were 1383 and 683, respectively, which represented a reduction of 50% (including delayed sessions) that allowed our reorganization process. CONCLUSIONS: To conserve resources during the pandemic, we successfully reduced the number of patients receiving treatment in a proactive fashion and adapted our organization to minimize the risk of COVID-19 contamination. Departments across the world may benefit from this same approach.

Repeated courses of low-dose 2 × 2 Gy radiation therapy in patients with indolent B-cell non-Hodgkin lymphomas.

PURPOSE: In patients with indolent B-cell non-Hodgkin's lymphoma (B-NHL), one course of low-dose radiotherapy (LD-RT) 2 × 2 Gy is emerging as new option of therapy in palliative setting. Efficacy of LD-RT when repeated remains to be determinate. This study aims to assess the efficacy of repeated LD-RT given in patients with indolent B-NHL. MATERIALS AND METHODS: All consecutive adult patients who received two or more courses of LD-RT 2 × 2 Gy for indolent B-NHL at Gustave Roussy institution, during the period 1990-2015 were retrospectively investigated. RESULTS: Thirty-three patients received two or more courses of LD-RT for indolent B-NHL during the study period. The median age was 57 (range 37-80) years, histological types were distributed among follicular lymphoma (n = 24 pts; 73%), marginal-zone lymphoma (n = 6 pts; 18%), and primary cutaneous follicle center lymphoma (n = 3 pts; 9%). The median number of low-dose radiation therapy courses given per patients was 2 (range 2-6). The overall response rates following the first and the second course of LD-RT were 96% and 88%, respectively (P = .31). The 1- and 2-years local control rates following the first courses of LD-RT were 94% (CI 95: 86-100) and 94% (CI 95: 86-98); and were 91% (CI 95: 82-100) and 88% (CI 95: 77-100) following the second course of LD-RT (P = .39). CONCLUSION: The repeated courses of LD-RT offered similar efficacy compare with the first course in patients with indolent B-NHL. LD-RT repeated is a simple, easy to give, and non-toxic asset that could be investigated as treatment option in patients with indolent B-NHL.

Induction chemotherapy followed by radiotherapy for N3 head and neck squamous cell carcinoma.

BACKGROUND: The treatment outcomes for N3 HNSCC treated with induction chemotherapy (ICT) followed by definitive radiation were reported to clarify the role of ICT and potential prognostic factors. METHODS: A retrospective study was conducted on 120 patients with N3 (≥6 cm) HNSCC, who were treated with ICT as initial treatment. Survival outcomes and potential prognostic factors were reported. RESULTS: The response rate to ICT was 68.3%. There was a statistically significant difference between responders and non-responders in terms of 5-year OS (35.1% vs 13.3%, P < .001) and PFS (29.4% vs 7.4%, P < .001). Good response to ICT (P < .001) and upfront neck dissection (UFND) before radiotherapy (P = .016) were factors predicting for better OS. However, UFND before radiotherapy was not associated with improved outcomes among responders. CONCLUSIONS: This study suggests that ICT could be one treatment option for N3 HNSCC. Among responders to ICT, UFND before radiotherapy could be avoided.

Neutrophilia as prognostic biomarker in locally advanced stage III lung cancer.

OBJECTIVE: To study the prognostic value of baseline leukocytosis or neutrophiliain two retrospective cohorts of stage III Non-Small Cell Lung Cancer (NSCLC) patients. MATERIALS AND METHODS: Clinical records of consecutive previously untreated NSCLC patients in our Institution between June 2001 and September 2016 for stage III NSCLC were collected. The prognostic value of pretreatment leucocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophil count exceeding 10 and 7 G/L, respectively. RESULTS: We identified 238 patients, displaying baseline leukocytosis or neutrophilia in 39% and 40% respectively. Most were diagnosed with adenocarcinoma (48%), and stage IIIB NSCLC (58%). 3-year actuarial overall survival (OS) and progression-free survival (PFS) were 35% and 27% respectively. Local relapses were reported in 100 patients (42%), and distant metastases in 132 patients (55%). In multivariate analysis, leukocytosis, neutrophilia, and induction chemotherapy regimen based on carboplatin/paclitaxel were associated with worse OS and PFS (p<0.05). Neutrophilia independently decreased Locoregional Control (LRC) (HR = 2.5, p<0.001) and Distant Metastasis Control (DMC) (HR = 2.1, p<0.001). Neutrophilia was significantly associated with worse brain metastasis control (p = 0.004), mostly in adenocarcinoma patients (p<0.001). CONCLUSION: In stage III NSCLC patients, treated with concurrent cisplatin-based chemoradiation, baseline leukocytosis and neutrophilia were associated with worse OS, PFS, LRC, and DMC. In addition with previously available markers, this independent cost-effective biomarker could help to stratify stage III NSCLC population with more accuracy.

[Hodgkin lymphoma: Current and future therapeutic strategies]. / Le lymphome de Hodgkin : stratégies thérapeutiques actuelles et futures.

Hodgkin lymphoma (HL) is a cancer that mostly affects young people, in which modern therapeutic strategies using chemotherapy and radiotherapy result in a cure rate exceeding 80%. Survivors are exposed to long-term consequences of treatments, such as secondary malignancies and cardiovascular diseases, whose mortality exceeds the one of the disease itself, with long-term follow-up. The current therapeutic strategy in HL, based on the assessment of initial risk factors, is the result of large clinical trials led by the main international cooperating groups. More recently, several groups have tried to develop treatment strategies adapted to the response to chemotherapy, evaluated by interim PET/CT scan. However to date, the combined treatment with chemotherapy followed by radiation therapy remains a standard in most of the above-diaphragmatic localized forms. Immune checkpoint inhibitors, and especially anti-PD1 antibodies, have shown dramatic results in some serious forms of relapsed or refractory HL, with limited toxicity, and may contribute in the future to reduce the toxicities of treatments.

Prognostic value of tumor mutations in radically treated locally advanced non-small cell lung cancer patients.

INTRODUCTION: Chemo-radiation is standard treatment in locally advanced non-small cell lung cancers (NSCLC). The prognostic value of mutations has been poorly explored in this population. RESULTS: Clinical data were collected from 190 patients and mutational profiles were obtained in 78 of them; 58 (74%) were males, 31 (40%) current smokers, 47/31 stage IIIA/IIIB and 40 (51%) adenocarcinoma. The following mutations were identified: EGFR 12% (9/78), KRAS 15% (12/78), BRAF 5% (3/65), PI3KCA 2% (1/57), NRAS 3% (1/32), and ALK+ (FISH) 4% (2/51). HER2 was not detected. Median follow-up was 3.1 years. Overall survival was evaluated by group; no significant differences were identified in median overall survival (p = 0.21), with 29.4 months for the EGFR/ALK group (n = 11), 12.8 months for other mutations (n = 17), and 23.4 months for wild-type (n = 50). The EGFR/ALK and other mutations groups had poorer median progression-free survival (9.6 and 6.0 months) compared to the wild-type group (12.0 months; multivariate hazard ratio 2.0 [95% CI, 0.9-4.2] and 2.8 [95% CI, 1.5-5.2] respectively, p = 0.003). MATERIALS AND METHODS: We retrospectively reviewed all patients receiving radical treatment for locally advanced NSCLC in a single institution between January 2002 and June 2013. Next generation sequencing was performed on DNA from paraffin-embedded tissue. ALK rearrangements were detected by immunohistochemistry and/or FISH. Mutational prognostic value for Kaplan-Meier survival parameters was determined by log-rank tests and Cox proportional hazards models. CONCLUSIONS: Selected gene alterations may be associated with poorer progression-free survival in locally advanced radically treated NSCLC and their prognostic and/or predictive value merits further evaluation in a larger population.