[French national standard for the treatment of squamous cell carcinoma of upper aero-digestive tract - General principles of treatment]. / Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures ­ Principes généraux de traitement.

OBJECTIVES: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations. METHODOLOGY: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS). RESULTS: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey. CONCLUSION: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field.

Correlation Between Serum and Urine Biomarkers and the Intensity of Acute Radiation Cystitis in Patients Treated With Radiation Therapy for Localized Prostate Cancer: Protocol for the Radiotoxicity Bladder Biomarkers (RABBIO) Study.

BACKGROUND: Despite improvements in radiation techniques, pelvic radiotherapy is responsible for acute and delayed bladder adverse events, defined as radiation cystitis. The initial symptoms of bladder injury secondary to pelvic irradiation are likely to occur during treatment or within 3 months of radiotherapy in approximately 50% of irradiated patients, and have a significant impact on their quality of life. The pathophysiology of radiation cystitis is not well understood, particularly because of the risk of complications associated with access to bladder tissue after irradiation, which limits our ability to study this process and develop treatments. OBJECTIVE: It is an original study combining digital data collection to monitor patients' symptoms and biological markers during irradiation. The main objective of our study is to evaluate the correlation of biological biomarkers with the intensity of acute radiation cystitis and the quality of life of patients, assessed with the digital telemonitoring platform Cureety. METHODS: Patients with intermediate-risk localized prostate cancer who are eligible for localized radiotherapy will be included. Inflammatory biomarkers will be analyzed in urine and blood samples before the start of radiotherapy and at weeks 4, 12, and 48 of irradiation, through quantitative methods such as a multiplex Luminex assay, flow cytometry, and enzyme-linked immunosorbent assay. We will also characterize the patients' gut and urine microbiota composition using 16S ribosomal RNA sequencing technology. Between sample collection visits, patients will complete various questionnaires related to radiation cystitis symptoms (using the International Prostate Symptom Score), adverse events, and quality of life (using the Functional Assessment of Cancer Therapy-Prostate questionnaire), using the Cureety digital remote monitoring platform. Upon receipt of the questionnaires, an algorithm will process the information and classify patients in accordance with the severity of symptoms and adverse events reported on the basis of Common Terminology Criteria for Adverse Events and International Prostate Symptom Score standards. This will allow us to correlate levels of urinary, blood, and fecal biomarkers with the severity of acute radiation cystitis symptoms and patient-reported quality of life. RESULTS: The study started in March 2022. We estimate a recruitment period of approximately 18 months, and the final results are expected in 2024. CONCLUSIONS: This prospective study is the first to explore the overexpression of inflammatory proteins in fluid biopsies from patients with symptoms of acute radiation cystitis. In addition, the 1-year follow-up after treatment will allow us to predict which patients are at risk of late radiation cystitis and to refer them for radioprotective treatment. The results of this study will allow us to develop strategies to limit radiation damage to the bladder and improve the quality of life of patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05246774; https://clinicaltrials.gov/ct2/show/NCT05246774?term=NCT05246774. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38362.

Effectiveness of a digital telemonitoring platform for cancer care of older patients: The ConnectElderlyPatientToDoctor study.

While telemedicine has been shown to improve the quality of care for cancer patients, it remains underused for older patients (OP), partly due to the assumption that OPs are unabled or unwilling to use digital tools. However, more than 50% of new cancers are diagnosed in people over 70. The ConnectElderlyPatientToDoctor study aimed to evaluate the OP compliance with the use of the digital telemonitoring platform Cureety in oncology. All cancer patients followed at the Military Hospital Bégin were eligible for the study. Patients were invited to respond to a symptomatology questionnaire personalized to their pathology and treatment. An algorithm evaluated the health status of the patient based on the reported adverse events. The population was divided into two groups, OP and younger patients (YP), based on a cut-off at 70 years. The primary endpoint was to assess the compliance of OPs with the use of the digital oncology platform Cureety, compared to YP. From July 2020 to September 2021, a total of 117 patients were included in our study. We found that 66% of the patients were compliant, with no difference between the two groups (71.2% of YP, 61.7% of OP, P = .29). In OPs, progression free survival (PFS) ratio at 6-months was 64.6% in the tolerant patients vs 23.4% in the nontolerant patients (HR = 0.1980, 95% CI = 0.04431-0.8845, P = .0339). The median PFS was 23.3 months in the tolerant group vs 3.3 months in the nontolerant group (P = .0339). The data of overall survival are immature. OPs had a clear benefit from using this platform, similar to what was observed for YP. Patients felt less isolated and felt that they benefited from personalized care with early ambulatory medical care of adverse events. We also found that the health indicators collected with the platform in the first month of treatment are predictive of the progression of the disease. This solution makes it possible to streamline and improve the care pathway of OP.

Prognostic factors of toxicity of immune checkpoint inhibitors in nonsmall cell lung cancer and small cell lung cancer patients: The ToxImmune study.

BACKGROUND: Immunotherapy alone or in combination has clearly improved the survival of patients with lung cancer. However, it may also be responsible for adverse events impacting these patients' quality of life. The ToxImmune study aims to identify prognostic factors that can help to predict immune-related adverse events. METHODS: We included all patients aged 18 years and older who had received at least one dose of immune checkpoint inhibitors, with or without other therapy, between June 2015 and December 2020 and were diagnosed with nonsmall cell lung cancer or small-cell lung cancer. Patients' baseline demographic characteristics, biological blood markers, and imaging by PET-scanner were collected from electronic medical records. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Events V.5.0). RESULTS: Sixty-four patients were included, of whom 60 (94%) presented at least one irAE. The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and grade 3-4 was 34% and 8% respectively. Female sex, Primitive Tumor Standardized Uptake Value Max (SUVmax) <5, number of metastases ≥3 and immunotherapy received after the first line were found to be significant risk factors for immune-related adverse events. Based on the number of risk factors, the ToxImmune score predicts the risk of having a grade ≥2 adverse event (primitive tumor SUV ≥ 5 = 0 vs. primitive tumor SUV <5 = 1, number of metastases <3 = 0 vs. number of metastases ≥3 = 1 and L1 = 0 vs. L1 ≥ 1). The incidence of grade ≥2 adverse events was 20%, 55% and 90% with ToxImmune scores 0, 1 and = 2 respectively (p = .003). Median progression-free survival (PFS) times were 19.2 months, 6.64 months and 2.63 months for ToxImmune scores 0, 1 and = 2 respectively, p = .13. Median overall survival times were 22.6 months, 16.4 months and 9.8 months for ToxImmune scores 0, 1 and ≥2 respectively, p = .24. The disease control rate (DRR) was 78% in ToxIummune score 0 group, and 50% in ToxImmune score 1 and ≥2 groups (p = .363). CONCLUSION: The ToxImmune score, which is grounded on objective clinical parameters, indicates that cases with a high score had an advanced threat of severe adverse events. The ToxImmune score could therefore be used in clinical practice to identify patients treated for lung cancer with immunotherapy and at risk of severe AE.

Educative Impact of Automatic Delineation Applied to Head and Neck Cancer Patients on Radiation Oncology Residents.

To evaluate the educational impact on radiation oncology residents in training when introducing an automatic segmentation software in head and neck cancer patients regarding organs at risk (OARs) and prophylactic cervical lymph node level (LNL) volumes. Two cases treated by exclusive intensity-modulated radiotherapy were delineated by an expert radiation oncologist and were considered as reference. Then, these cases were delineated by residents divided into two groups: group 1 (control group), experienced residents delineating manually, group 2 (experimental group), young residents on their first rotation trained with automatic delineation, delineating manually first (M -) and then after using the automatic system (M +). The delineation accuracy was assessed using the Overlap Volume (OV). Regarding the OARs, mean OV was 0.62 (SD = 0.05) for group 1, 0.56 (SD = 0.04) for group 2 M - , and 0.61 (SD = 0.03) for group 2 M + . Mean OV was higher in group 1 compared to group 2 M - (p = 0.01). There was no OV difference between group 1 and group 2 M + (p = 0.67). Mean OV was higher in the group 2 M + compared to group 2 M - (p < 0.003). Regarding LNL, mean OV was 0.53 (SD = 0.06) in group 1, 0.54 (SD = 0.03) in group 2 M - , and 0.58 (SD = 0.04) in group 2 M + . Mean OV was higher in group 2 M + for 11 of the 12 analysed structures compared to group 2 M - (p = 0.016). Prior use of the automatic delineation software reduced the average contouring time per case by 34 to 40%. Prior use of atlas-based automatic segmentation reduces the delineation duration, and provides reliable OARs and LNL delineations.

Beyond Surgical Treatment in Adenoid Cystic Carcinoma of the Head and Neck: A Literature Review.

Introduction: Adenoid cystic carcinoma (AdCC) is a rare tumour as it accounts for about 10% of all salivary gland neoplasms. It occurs in all age groups with a predominance of women, but no risk factors have been identified to date. Although AdCC behaves as a slow-growing tumour, it is characterized by multiple and late recurrences. Therefore, we aim to update the knowledge of the treatment options in advanced and recurrent cases. Materials and Methods: We performed a systematic literature review to provide a synthesis of the practical knowledge required for AdCC non-surgical management. Altogether, 99 out of the 1208 available publications were selected for analysis. Results: AdCC is described as a basaloid tumour consisting of epithelial and myoepithelial cells. Immunohistochemistry is useful for diagnosis (PS100, Vimentin, CD117, CKit, muscle actin, p63) and for prognosis (Ki67). Identified mutations could lead to therapeutic opportunities (MYB-NFIB, Notch 1). The work-up is mainly based on neck and chest CT scan and MRI, and PET-CT with 18-FDG or PSMA can be considered. Surgical treatment remains the gold standard in resectable cases. Post-operative intensity modulated radiotherapy is the standard of care, but hadron therapy may be used in specific situations. Based on the available literature, no standard chemotherapy regimen can be recommended. Conclusion: There is currently no consensus on the use of chemotherapy in AdCC, either concomitantly to RT in a postoperative setting or at a metastatic stage. Further, the available targeted therapies do not yet provide significant tumour response.

The Use of Telemedicine in Cancer Clinical Trials: Connect-Patient-to-Doctor Prospective Study.

BACKGROUND: Telemedicine is currently being adopted for the management of patients in routine care. However, its use remains limited in the context of clinical trials. OBJECTIVE: This study aimed to demonstrate the feasibility of telemonitoring and patient-reported outcomes collection in the context of clinical trials. METHODS: The patients who were included in an interventional oncology clinical trial were eligible. The patients were registered with a digital tool to respond to a patient-reported outcomes questionnaire (ePRO) based on CTCAE (The Common Terminology Criteria for Adverse Events, National Cancer Institute), version 5.0, personalized to their pathology and treatment. An algorithm evaluated the health status of the patient based on the reported adverse events, with a classification in 4 different states (correct, compromise, state to be monitored, or critical state). The main objective was to evaluate the feasibility of remote monitoring via a connected platform of patients included in a clinical trial. RESULTS: From July 1, 2020, to March 31, 2021, 39 patients were included. The median age was 71 years (range 41-94); 74% (n=29) were male, and 59% (n=23) had metastatic disease. Out of the 969 ePRO questionnaires completed over the course of the study, 77.0% (n=746) were classified as "correct," 10.9% (n=106) as "compromised," and 12.1% (n=117) as "to be monitored" or "critical." The median response time was 7 days (IQR 7-15.5), and 76% (25/33) of the patients were compliant. Out of the 35 patients who answered a satisfaction questionnaire, 95% (n=33) were satisfied or very satisfied with the tool, and 85% (n=30) were satisfied with their relationship with the health care team. There were 5 unscheduled hospitalizations during the study period. CONCLUSIONS: Remote monitoring in clinical trials is feasible, with a high level of patient participation and satisfaction. It benefits patients, but it also ensures the high quality of the trial through the early management of adverse events and better knowledge of the tolerance profile of experimental treatments. This e-technology will likely be deployed more widely in our clinical trials.

The Role of Cost-Effectiveness Analysis in Patient-Centered Cancer Care in the Era of Precision Medicine.

Over the last few decades, changes in diagnostic and treatment paradigms have greatly advanced cancer care and improved outcomes [...].

Local ablative therapy in oncogenic-driven oligometastatic non-small cell lung cancer: present and ongoing strategies-a narrative review.

Oligometastatic (OM) disease is defined by a low metastatic tumor spread. OM non-small cell lung cancer (NSCLC) treatment aims to improve the patient's prognosis and quality of life, in an attempt-to-cure objective. Oncogenic-driven metastatic NSCLC accounts for about 20-25% of NSCLCs, with an ever-increasing number of potentially druggable molecular alterations. Due to specific targeted therapy, the care and prognosis of mutated NSCLC is quite different from non-oncogenic-driven NSCLC. However, OM-NSCLC treatment guidelines do not specifically discuss oncogenic-driven OM-NSCLC patients. We conducted a narrative review regarding retrospective and prospective studies published from inception to May 2020 dealing with oncogenic-driven OM-NSCLC in order to: (I) describe the specific patterns of metastatic spread of oncogenic-driven NSCLC (i.e., bone and pleural tropism in EGFR mutated NSCLC and serous and brain metastases in ALK NSCLC); (II) review the low level of current evidence for local ablative therapy (LAT) strategies in patients with oncogenic-driven OM-NSCLC, focusing on the benefit/risk of tyrosine kinase inhibitors (TKI) and LATs combination and (III) present strategies to help to select the best candidate for an attempt-to-cure approach. Finally, the optimal strategy may be to introduce a targeted therapy, then treat all tumor sites with LAT, and finally continue TKI for unknown prolonged duration in an attempt to prolong progression free survival in most patients, improve overall survival for some patients, and potentially lead to a cancer cure for a few patients.

Predictive Value of Neutrophils Count for Local Tumor Control After Chemoradiotherapy in Patients With Locally Advanced Pancreatic Carcinoma.

PURPOSE: Baseline neutrophil count may predict overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS: The international multicenter randomized LAP07 phase 3 trial has enrolled 442 patients with LAPC. We analyzed the prognostic value of both baseline neutrophilia (neutrophil count >7 g/L) and elevated or increasing neutrophil count as (1) neutrophilia or (2) increased absolute neutrophil count after induction chemotherapy versus baseline for OS, progression-free survival, and local control (LC). A Cox proportional hazard model was used to assess elevated or increasing neutrophil count status by randomly assigned treatment interactions for each endpoint. RESULTS: Among the 442 patients, 47 patients (11%) with baseline neutrophilia had worse OS (median 8.9 vs 13.3 months; P = .01). After induction chemotherapy, among the 235 patients whose blood counts were available, 90 patients (38%) had elevated or increasing neutrophil count associated with poorer OS in univariate (median 14.4 vs 17.9 months; P = .001) and multivariate analysis (P = .004). Elevated or increasing neutrophil count was also predictive of a decreased benefit of chemoradiation therapy on LC. In 126 patients without elevated or increasing neutrophil count, 1-year LC was 80% in the chemoradiation arm versus 54% in the chemotherapy arm (P < .001; interaction test P = .015). CONCLUSIONS: In this study, baseline neutrophilia and increased absolute neutrophil count were associated with worse OS in this large series of patients with LAPC. In addition, the counts were an independent prognosis factor and a strong predictive LC biomarker for chemoradiation therapy benefit. An assessment of neutrophils counts can help to improve the selection of patients who might benefit from chemoradiation therapy after induction chemotherapy.

Evaluation of medical practices in oncology in the context of the COVID-19 pandemic in France: Physicians' point of view: the PRATICOVID study.

The cancer population seems to be more susceptible to COVID-19 infection and have worse outcomes. We had to adapt our medical practice to protect our patients without compromising their cancer prognosis. The national PRATICOVID study aims to describe the adaptation of cancer patient care for this population. We analyzed data from nine different institutions. The primary endpoint was to assess the prevalence of adapted patient care during the pandemic. The secondary endpoints were to describe the point of view of clinicians and patients during and after the pandemic. We analyzed 435 medical procedures between 9th of March and 30th of April. Because of the COVID-19 pandemic, 47.6% of the outpatients received modified patient care. Twenty-four percent of scheduled surgeries were postponed, or were performed without perioperative chemotherapy, 18.4% followed a hypofractioned schedule, and 57% had an adaptive systemic protocol (stopped, oral protocol, and spacing between treatments). Seventy percent of physicians used telemedicine. During this period, 67% of the physicians did not feel distressed taking care of their patients. However, 70% of physicians are worried about the aftermath of the lockdown, as regards future patient care. The PRATICOVID study is the first to assess modification of patient care in cancer outpatients during an epidemic. With this unprecedented crisis, physicians were able to adapt their practice in order to protect their patients against the virus while ensuring continuity of patient care. But physicians are worried about the aftereffects of the lockdown specifically in regard to care pathway issues.

Incorporating Magnetic Resonance Imaging (MRI) Based Radiation Therapy Response Prediction into Clinical Practice for Locally Advanced Cervical Cancer Patients.

In recent years, magnetic resonance imaging (MRI) has become one of the standard imaging tools to define the macroscopic gross tumor volume in locally advanced cervical cancer patients based on T2-weighted sequence. Recent data suggest that functional MRI could be used to potentially improve the delineation of target volumes based on physiologic features, defining radioresistant subvolumes that may require higher doses to achieve local cure. Functional imaging can be used to predict tumor biology and outcome, as well as for assessment of tumor response during radiotherapy. The concept of adaptive radiotherapy relies on the possibility of monitoring variations in target volumes structures to guide treatment-plan modification during radiotherapy, taking into account not only internal movements but also tumor response. With integrated MRI in radiotherapy linear accelerators, motion monitoring during treatment delivery has become available. MRI can be also used to accurately evaluate cervical tumor residual volume after chemoradiotherapy, and therefore allowing a personalized treatment planning for brachytherapy boost, based on tumor radiosensitivity. In this review, we discuss how MRI tumor response assessment could be included into clinical practice during radiation therapy in locally advanced cervical cancer patients.

Metformin: (future) best friend of the radiation oncologist?

Several molecules are being investigated for their ability to enhance the anti-tumor effect of radiotherapy. The widely prescribed antidiabetic drug metformin has been suggested to possess anti-cancer activity; data indicate that metformin could also enhance radiation sensitivity. The purpose of this review is to summarize current knowledge on the specific effect of metformin in the field of RT, while also discussing the many unknowns that persist. Preclinical models point to multiple mechanisms involved in the radiosensitizing effects of metformin that are mainly linked to mitochondrial complex I inhibition and AMP-activated protein kinase. Transposition of results from bench to bedside will be discussed through the lens of the drug concentration, its potential limits in human settings, and possible alternatives. Clinical data suggest metformin improves progression-free and overall survival in patients for many different cancers treated with RT; nevertheless, the results are not always consistent. The main limitations of the reviewed literature are the retrospective nature of studies, and most of the time, a lack of information on MTF treatment duration and the administered dosages. Despite these limitations, the possible mechanisms of the role of metformin and its utility in enhancing radiotherapy treatments are analyzed. Ongoing clinical trials are also discussed.

Interaction between the Number of Chemotherapy Cycles and Brachytherapy Dose/Volume Parameters in Locally Advanced Cervical Cancer Patients.

Scarce data exist on concurrent chemotherapy in locally advanced cervical cancer (LACC) patients (pts) treated with image-guided adaptive brachytherapy (IGABT). We examined the effect of a number of chemotherapy cycles and their interaction with brachytherapy dose/volume parameters. Clinical records of 209 consecutive pts treated for a LACC were reviewed. Pts received CRT concurrently with cisplatin 40 mg/m² or carboplatin AUC2. An additional cycle could have been delivered during the pulse-dose rate (PDR)-IGABT. The impact of a number of chemotherapy cycles on outcome was examined, as well as the interactions with dose volume parameters. The number of cycles was four in 55 (26.3%) pts, five in 154 (73.7%) including 101 receiving the fifth cycle during IGABT. Median follow-up was 5.5 years. Pts receiving five cycles had a better outcome on all survival endpoints, including three year local control rate (93.9% vs. 77.2%; p < 0.05). In the subgroup, only pts with tumor FIGO (Fédération Internationale de Gynécologie Obstétrique) stage ≤IIB or with CTVHR > 25 cm3 had a better outcome. Pts receiving four cycles with D90CTVHR > 80GyEQD2 had the same locoregional control-(LRC) as those receiving five cycles and achieving D90CTVHR ≤ 80 GyEQD2 (p = 0.75). An optimal propensity score matching the balance for the FIGO stage, CTVHR volume and D90CTVHR confirmed the effect, with the largest life expectancy benefit for locoregional failure-free survival (absolute gain: 1.5 years; p = 0.017). Long-term radiation-induced toxicity was not increased. Increasing the total number of cycles from 4 to 5 improved LFS, suggesting a place for systemic strategies aimed at in-field cooperation. Delivering an additional cycle at the time of brachytherapy did not increase morbidity and there permitted an increase in chemotherapy dose intensity.

Esophageal brachytherapy: Institut Gustave Roussy's experience.

PURPOSE: Esophageal cancer is characterized by its propension to local evolution, which conditions prognosis and quality of life. Brachytherapy may be a therapeutic option for all stages of esophageal cancer. METHODS AND MATERIALS: This retrospective unicentric study included all consecutive patients treated for an esophageal high-dose-rate brachytherapy in our institution from 1992 to 2018. RESULTS: Ninety patients were included. They were treated in four distinct indications: exclusive (7 patients), boost after external beam radiotherapy (41), reirradiation (36), or palliative aim (6). Most frequently prescribed schemes were 3 × 5 Gy (boost) or 6 × 5 Gy (exclusive treatment and reirradiation) at applicator's surface or at 5 mm. At the end of follow-up, 50% of patients had presented with local recurrence. Seventeen percent of patients had a metastatic relapse. Median overall survival was 15 months in the whole cohort: 22 months in the boost setting, 25 months for exclusive brachytherapy, 15 months for reirradiation, and only 2 months for palliative treatment. Tumor length at brachytherapy, brachytherapy dose, and interfraction response were significantly associated to overall survival. 40% of patients presented with grade 2+ toxicity, mostly esophagitis, including three toxic deaths. CONCLUSIONS: Although local control outcomes are still poor, one must remember that patients are unfit for any curative therapeutic option and that palliative chemotherapy offers mediocre results. The most promising setting probably is reirradiation because brachytherapy offers a remarkable dose gradient allowing best organ at risk sparing, with an encouraging rate of long survivors (19% at 2 years). Esophageal brachytherapy deserves to be further investigated because some patients, even unfit, may benefit from it, with acceptable toxicity.

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.

Solitary Plasmacytoma Treated by Lenalidomide-Dexamethasone in Combination with Radiation Therapy: Clinical Outcomes.

PURPOSE: The study evaluates the results of the concurrent use of lenalidomide-dexamethasone with intensity modulated radiation therapy (IMRT) for solitary plasmacytoma in terms of toxicity and outcome. METHODS AND MATERIALS: Forty-six patients were treated for histologically proven solitary plasmacytoma (SP) between June 2007 and June 2018 in our Department (Curie Institute, Paris, France). All patients received IMRT. The median total dose was 40 Gy (range, 40-46). Prescription of concurrent lenalidomide-dexamethasone with radiation therapy was left to the discretion of the referring hematologist-oncologist and started the first day of radiation therapy for 4 cycles. RESULTS: Twenty-seven solitary plasmacytoma were treated with IMRT alone and 19 with lenalidomide-dexamethasone in association with IMRT. At 5 years, the local control, multiple myeloma-free survival (MMFS), and progression-free survival (PFS) rates were 96.3%, 85.4%, and 60%. MMFS and PFS were significantly higher in the IMRT plus lenalidomide-dexamethasone group compared with IMRT alone group (100% vs 77.1%, P = .02 and 81.7% vs 48.4%, P = .047, respectively). No major toxicity was found in either group. CONCLUSIONS: Lenalidomide-dexamethasone in association with IMRT in the treatment of solitary plasmacytoma is safe and improves MMFS and PFS. Further prospective and comparative studies are needed to confirm these results.

Clinical and economic burden of head and neck cancer: a nationwide retrospective cohort study from France.

OBJECTIVES: To evaluate the clinical and economic burden of head and neck squamous cell carcinoma (HNSCC) in France. METHODS: All 53,255 incident adult patients discharged with a first diagnosis of HNSCC in 2010-2012 were identified from the 2008-2013 French National Hospital Discharge (PMSI) database. We conducted a retrospective longitudinal analysis of prognosis and direct costs attributable to HNSCC. RESULTS: Direct medical costs attributable to HNSCC care amounted to 665 million euros in 2012 in France. The majority (62%) of incident patients were 64 years old or less at HNSCC diagnosis and incurred 1.3-fold higher mean direct costs as compared to elderly patients (41,909 vs 32,221 euros over 3 years, respectively; p<0.001). HNSCC stage at initial treatment was the major driver of mean (SD) direct costs over 3 years (p<0.001): 19,819 (23,150) euros in 31% patients diagnosed at early stage; 46,791 (34,841) euros in 60% patients diagnosed at locally advanced stage; and 43,377 (33,953) euros in 9% patients diagnosed with distant metastasis. About half patients died over 3 years at a median (IQR) age of 63 (56-75) years resulting in 10.9 years-of-life lost on average per incident patient. CONCLUSION: The present study suggests that the clinical and economic burden of HNSCC is substantial in France.

Increased bone marrow SUVmax on 18F-FDG PET is associated with higher pelvic treatment failure in patients with cervical cancer treated by chemoradiotherapy and brachytherapy.

The aim of this study was to evaluate if bone marrow (BM) SUVmax measured on pre-treatment 18F-FDG PET/CT predicts the clinical outcome of locally advanced cervical cancer (LACC). We recruited retrospectively patients with LACC who underwent staging 18F-FDG PET/CT and had baseline blood tests, then treated by chemoradiation therapy (CRT), followed by image-guided adaptive brachytherapy (IGABT). BM SUVmax was calculated and correlated to inflammatory blood markers. Tumor size and pelvic lymph node involvement were evaluated on baseline MRI. Prognostic value of SUV uptake and blood markers regarding overall survival (OS), pelvic and extra-pelvic recurrence-free survival (PRFS and EPRFS respectively) was assessed using Cox models with adjusted p-values. 116 patients with FIGO stage Ib-IVa cervical cancer, treated between 2005 and 2014, were analyzed. The median follow-up was 75.5 months. BM SUVmax was significantly correlated to tumor SUVmax. In multivariate analysis, PRFS was significantly poorer in patients with high BM SUVmax (>2.8) and neutrophilia (p < .05). Tumor size (>5 vs ≤5 cm) could predict PRFS, EPRFS and OS (p < .05). In our cohort, FIGO stage (I-II vs III-IV), pelvic lymph node involvement and tumor SUVmax (>12 vs ≤12) were not prognostic for OS or pelvic and extra-pelvic relapses. Patients with LACC and high BM SUVmax on 18F-FDG PET have worse PFRS following CRT plus IGABT. These results can be potentially explained by the pro-inflammatory role of the tumor microenvironment and G-CSF expressed by tumor cells. These data support the role of PET as a potential indicator of disease aggressiveness beyond tumor staging.