Cost-effectiveness of weekly adaptive radiotherapy versus standard IMRT in head and neck cancer alongside the ARTIX trial.

BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. Objective: To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. Design, Setting, and Participants: This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022. Interventions: The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning). Main Outcomes and Measures: The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival. Results: A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms. Conclusions and Relevance: This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates. Trial Registration: ClinicalTrials.gov Identifier: NCT01874587.

Outcomes and Side Effects of Preoperative Chemoradiotherapy for Locally Advanced Upper Rectal Cancer.

BACKGROUND/AIM: The benefit of neoadjuvant (chemo) radiotherapy for locally advanced upper rectal tumors remains controversial. Thus, we aimed to evaluate the outcome of patients with stage II or-III upper rectal cancer undergoing neoadjuvant (chemo) radiotherapy followed by total mesorectal excision in our institution. PATIENTS AND METHODS: From April 2004 to October 2019, all patients with stage II or III upper rectal cancer treated with neoadjuvant (chemo) radiotherapy followed by total mesorectal excision were identified from our database. Overall survival, progression-free survival, and local recurrence were assessed using the Kaplan-Meier method. Acute and late treatment-related toxicities were recorded according to the CTCAE-5 version. RESULTS: The study group consisted of 106 patients. Respectively, 36% and 61% of patients had stage II and stage III upper rectal cancer. The median follow-up period was 4.4 ± 3.4 years. Five-year overall survival and progression-free survival were respectively 78% [95% confidence interval (CI)=69.2-88] and 76.8% (95%CI=68.4-86.2). The rate of local recurrence at 5 years was 3.78% (95%CI=0-7.98). Forty-two percent of patients presented early toxicities and 27.4% of patients experienced early surgical complications. Late toxicities and surgical complications occurred in 24.5% and 9.4% of patients, respectively. CONCLUSION: Neoadjuvant (chemo) radiotherapy followed by total mesorectal excision of stage II-III upper rectal cancer is effective and safe.

[National meetings for complex cases in pediatric radiation oncology: Back on six years experience]. / Réunions nationales de cas complexes en radiothérapie pédiatrique : retour sur six années d'expérience.

INTRODUCTION: Pediatric cancers are rare, representing almost 2,500 new cases each year in France meaning 1% of all cancers. Since 2012, a twice-monthly national web-based conference was held in France. Any patient with a pediatric type cancer requiring radiotherapy can be discussed. It aims at answering the physician with specific radiation therapy questions on rare and complex indications, at promoting the use of referential and the inclusion into clinical protocols. RESULTS: From 2012 to 2018, 1,078 cases were discussed for 940 patients in 142 meetings. Mean age was 10 years old (4 months to 45 years). The mean number of attendants was 6 (2 to 32). We review in this paper the main clinical features discussed in the web-conference and the decision of the web-conference. In 85% cases, the first treatment proposed was mostly accepted, but in 15%, other proposals were done (modifications of target volumes, doses or indications). CONCLUSIONS: Between 2012 and 2018, more than 1,000 pediatric irradiation cases were discussed in our web-based conference leading to 15% of change in radiation protocol. The rarity and the complexity of these situations need those meetings. They provide a place to improve the global knowledge and the quality of the treatments provided.

Simultaneous or staged resection for synchronous liver metastasis and primary rectal cancer: a propensity score matching analysis.

BACKGROUND: Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15-25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. METHODS: We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. RESULTS: There were 70 patients (55/15 males, female respectively) with median age 60 (54-68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). CONCLUSIONS: Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.

Impact of Modern Management Strategies on the Clinical Outcome of Patients With Low Rectal Cancer - A Retrospective, Monocentric Cohort Study.

BACKGROUND: The aim of this study was to retrospectively investigate the impact of intersphincteric resection (ISR) and Enhanced Recovery After Surgery (ERAS) protocols for rectal cancer. PATIENTS AND METHODS: Since we implemented rectal ERAS protocol and ISR in 2016, we retrospectively assessed and compared clinical, pathological and survival outcomes of two groups of patients: group 1, treated 2000-2015 (n=242); and group 2, treated 2016-2020 (n=108). Propensity score matching using nearest-neighbor method was used to match each patient of group 1 to a patient of group 2. RESULTS: Before and after matching, the American Society of Anesthesiology score for patients in group 1 was significantly lower than in group 2 (score of 3: 9.9% vs. 25.9%, p<0.0001) as were grade I-II complications (27.7% vs. 45.4% p<0.001). Before and after matching, the quality of the mesorectum excision was significantly lower in group 1 (complete in 31% vs. 59.2% p<0.0001). After matching, 3-year overall survival for groups 1 and 2 were similar (88.2% vs. 92.6%; p=0.988). CONCLUSION: ERAS and ISR had no negative impact on the oncological outcome of our patients and increased the preservation of bowel continuity.

Curative intent Stereotactic Ablative Radiation Therapy (SABR) for treatment of lung oligometastases from head and neck squamous cell carcinoma (HNSCC): a multi-institutional retrospective study.

OBJECTIVES: The aim of this retrospective study was to assess outcomes of SABR for metachronous isolated lung oligometastases from HNSCC. METHODS: For patients who developed isolated, 1 or 2 lungs lesions (<5cm) consistent with metastases from HNSCC, the indication of SABR was validated in a multidisciplinary tumor board. All patients were monitored by CT or PET CT after SABR (Stereotactic Ablative Body Radiation) for HNSCC. RESULTS: Between November 2007 and February 2018, 52 patients were treated with SABR for metachronous lung metastases. The median time from the treatment of the primary HNSCC to the development of lung metastases was 18 months (3-93). The cohort's median age was 65.5 years old (50-83). The vast majority (94.2%) received 60 Gy in three fractions. Forty-one patients (78.5%) presented a solitary lung metastasis, while 11 patients (21.5%) had two lung metastases. With a median follow-up of 45.3 months, crude local and metastatic control rates were 74 and 38%, respectively. 1 year and 2 year Overall Survival (OS) were 85.8 and 65.9%, respectively. The median OS was 46.8 months. About one-fourth of patients were retreated by SABR for distant pulmonary recurrence. The treatment was well tolerated with only one patient who reported ≥ grade 3 toxicity (1.9%). CONCLUSION: In selected metastatic HNSCC patients, early detection and treatment of lung metastases with SABR is effective and safe. Prospective studies are required to validate this potential shift. ADVANCES IN KNOWLEDGE: Patients with oligometastases and controlled primary HNSCC seem to benefit from metastasis directed therapies.

Prognostic Impact of Upfront Surgery for Locally Advanced Upper Rectal Adenocarcinoma.

BACKGROUND/AIM: Impact of neoadjuvant chemoradiotherapy (CRT) in locally advanced upper rectal adenocarcinoma (LAURC) is debated. The aim of this study was to compare outcomes between LAURC and locally advanced sigmoid and recto-sigmoid junction cancer (LASC). PATIENTS AND METHODS: This retrospective study included 149 consecutive patients [42 CRT/LAURC, 16 upfront surgery (US/LAURC) and 91 LASC]. Partial mesorectum excision (PME) was performed for all LAURC. Pathology results as well as short-and-long-term outcomes were compared between the three groups. RESULTS: Overall mortality was nil. Morbidity was comparable (CRT/LAURC 23.8% vs. LASC: 20.8% vs. US/LAURC: 37.5%, p=0.2354). CRT was associated with a reduced risk of positive circumferential margin (CRT/LAURC: 9.5% vs. US/LAURC: 18.7%, p<0.0001). Recurrence rate, 5-year disease-free survival and overall survival were similar between the three groups. CONCLUSION: CRT and PME did not improve LAURC oncological outcomes but were associated with improved margins. CRT for LAURC was not associated with increased morbidity.

Hypofractionated stereotactic body radiation therapy (SBRT) in pediatric patients: preliminary toxicity results of a national prospective multicenter study.

OBJECTIVES: While hypofractionated stereotactic body radiotherapy (SBRT) has been largely adopted in the adult setting, its use remains limited in pediatric patients. This is due, among other factors, to fear of potential toxicities of hypofractionated regimens at a young age. In this context, we report the preliminary acute (<3 months from SBRT) and middle-term (3-24 months) toxicity results of a national prospective study investigating SBRT in pediatric patients. METHODS: Between 2013 and 2019, 61 patients were included. The first 40 patients (median age: 12 y, range: 3-20) who completed a 2-year-follow-up were included in the present analysis. SBRT was used for treating lung, brain or (para)spinal lesions, either as first irradiation (35%) or in the reirradiation setting (65%). RESULTS: Acute and middle-term grade ≥2 toxicities occurred in 12.5 and 7.5% of the patients, respectively. No grade ≥4 toxicities occurred. Almost all toxicities occurred in the reirradiation setting. CONCLUSION: SBRT showed a favorable safety profile in young patients treated for lung, brain, and (para)spinal lesions. ADVANCES IN KNOWLEDGE: SBRT appeared to be safe in pediatric patients treated for multiple oncology indications. These results support further evaluation of SBRT, which may have a role to play in this patient population in the future.

Exclusive Hyperfractionated Radiation Therapy and Reduced Boost Volume for Standard-Risk Medulloblastoma: Pooled Analysis of the 2 French Multicentric Studies MSFOP98 and MSFOP 2007 and Correlation With Molecular Subgroups.

PURPOSE: Medulloblastoma has recently been characterized as a heterogeneous disease with 4 distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4, with a new definition of risk stratification. We report progression-free survival, overall survival, and long-term cognitive effects in children with standard-risk medulloblastoma exclusively treated with hyperfractionated radiation therapy (HFRT), reduced boost volume, and online quality control, and we explore the prognostic value of biological characteristics in this chemotherapy-naïve population. METHODS AND MATERIALS: Patients with standard-risk medulloblastoma were enrolled in 2 successive prospective multicentric studies, MSFOP 98 and MSFOP 2007, and received exclusive HFRT (36 Gy, 1 Gy/fraction twice daily) to the craniospinal axis followed by a boost at 68 Gy restricted to the tumor bed (1.5 cm margin), with online quality assurance before treatment. Patients with MYC or MYCN amplification were not excluded at the time of the study. We report progression-free survival and overall survival in the global population, and according to molecular subgroups as per World Health Organization 2016 molecular classification, and we present cognitive evaluations based on the Wechsler scale. RESULTS: Data from 114 patients included in the MSFOP 98 trial from December 1998 to October 2001 (n = 48) and in the MSFOP 2007 from October 2008 to July 2013 (n = 66) were analyzed. With a median follow-up of 16.2 (range, 6.4-19.6) years for the MSFOP 98 cohort and 6.5 (1.6-9.6) years for the MSFOP 2007 cohort, 5-year overall survival and progression-free survival in the global population were 84% (74%-89%) and 74% (65%-81%), respectively. Molecular classification was determined for 91 patients (WNT [n = 19], SHH [n = 12], and non-WNT/non-SHH [n = 60]-including group 3 [n = 9], group 4 [n = 29], and not specified [n = 22]). Our results showed more favorable outcome for the WNT-activated subgroup and a worse prognosis for SHH-activated patients. Three patients had isolated extra-central nervous system relapse. The slope of neurocognitive decline in the global population was shallower than that observed in patients with a normofractionated regimen combined with chemotherapy. CONCLUSIONS: HFRT led to a 5-year survival rate similar to other treatments combined with chemotherapy, with a reduced treatment duration of only 6 weeks. We confirm the MSFOP 98 results and the prognostic value of molecular status in patients with medulloblastoma, even in the absence of chemotherapy. Intelligence quotient was more preserved in children with medulloblastoma who received exclusive HFRT and reduced local boost, and intelligence quotient decline was delayed compared with patients receiving standard regimen. HFRT may be appropriate for patients who do not consent to or are not eligible for prospective clinical trials; for patients from developing countries for whom aplasia or ileus may be difficult to manage in a context of high cost/effectiveness constraints; and for whom shortened duration of RT may be easier to implement.

Neoadjuvant Treatment in Upper Rectal Cancer Does Not Improve Oncologic Outcomes But Increases Postoperative Morbidity.

BACKGROUND/AIM: Neoadjuvant chemoradiation/radiation therapy in locally advanced (LA) upper rectal adenocarcinoma management remains unclear. The aim of this study was to compare outcomes between neoadjuvant chemoradiation therapy (CRT) and upfront surgery (US). PATIENTS AND METHODS: A total of 127 patients were retrospectively included from 5 centers (79 treated with US and 48 with CRT). CRT and US groups were compared in terms of postoperative complications and long-term oncological and functional results. RESULTS: Total mesorectal excision (TME) was more frequent in CRT (58% vs. 20% in US, p<0.001). CRT was associated with more overall and severe postoperative complications (60% vs. 30%, p<0.001 and 17% vs. 1%, p=0.002, respectively), and was the only risk factor [OR=18.8 (2.2-160.2), p=0.007]. Five-year overall survival and 5-year recurrence-free survival were similar between CRT and US (96% vs. 91% p=0.256 and 85.4% vs. 85%, p=0.495). The functional results were similar between the two groups. CONCLUSION: CRT did not improve long-term oncological outcomes in patients with LA upper rectal adenocarcinoma, but increased postoperative complications compared with US.

Complete Pathological Response Following Radiochemotherapy for Locally Advanced Rectal Cancer: Short and Long-term Outcome.

BACKGROUND/AIM: Preoperative radiochemotherapy (RCT) followed by total mesorectum excision has become the gold standard for locally advanced carcinoma of the low and middle rectum. The aim of the study is to evaluate the short and long-term outcomes of patients in complete pathological response (PR) following this treatment sequence. PATIENTS AND METHODS: One hundred and thirty patients were retrospectively included between 2005 and 2017 in an expert centre, with 3 groups formed, according to the PR: i) complete PR (absence of tumour cells on the surgical specimen ypT0N0), ii) partial PR (T or N downsizing) and iii) without PR. RESULTS: The complete PR rate was 13.1%. The complete PR group tended to develop less symptomatic fistulas compared to partial PR and without PR groups (5.8% versus 13.5% versus 18.7, respectively; p=0.607). The 5-year disease-free survival was increased for complete-PR patients (93% versus 79% versus 47%, respectively; p=0.0003) without an improvement in overall survival. CONCLUSION: Complete PR is associated with an improvement in survival without recurrence and without an improvement in the overall survival at 5 years.

Re-irradiation of locally recurrent pediatric intracranial ependymoma: Experience of the French society of children's cancer.

PURPOSE: This study aimed to evaluate retrospectively the clinical results of re-irradiation for children with a locally recurrent brain ependymoma. METHODS: 33 full-dose re-irradiations were delivered to 31 children with a recurrent brain ependymoma after a standard treatment. Each child was followed up with clinical and MRI examinations. We evaluated overall survival, local recurrence free-survival and short term toxicity according to CTCAE 4.0 scale. RESULTS: With a median follow-up of 37 months (range, 0 to 107), median local recurrence free-survival was 31 months (range, 2 to 63) and median overall survival was 34 months (range, 3 to 63). It was significantly higher in patients who underwent surgery first, compared with re-irradiation only. Cumulated dosimetric data were available for 22 patients. On average, maximal BED to brain stem was 106,2 Gyα/ß3 (±35,4) for infratentorial re-irradiation. No acute toxicity grade >2 was reported and 1 case of brain radionecrosis treated successfully with steroids was reported after radiosurgery. CONCLUSION: Local recurrence of brain ependymoma can be treated with full-dose re-irradiation, which can be hypofractionated with an acceptable short term toxicity in spite of high total doses delivered to OARs, especially brain stem.

Hippocampal Sparing During Craniospinal Irradiation: What Did We Learn About the Incidence of Perihippocampus Metastases?

PURPOSE: To identify the incidence of patients with perihippocampal metastases to assess the risk of brain relapse when sparing the hippocampal area. Medulloblastoma (MB) represents 20% of pediatric brain tumors. For high-risk MB patients, the 3- to 5-year event-free survival rate has recently improved from 50% to >76%. Many survivors, however, experience neurocognitive side effects. Several retrospective studies of patients receiving whole brain irradiation (WBI) have suggested a relationship between the radiation dose to the hippocampus and neurocognitive decline. The hippocampal avoidance-WBI (HA-WBI) approach could partially reduce neurocognitive impairment in children treated for high-risk MB. METHODS AND MATERIALS: From 2008 to 2011, 51 patients with high-risk MB were treated according to the French trial primitive neuroectodermal tumor HR+5. Hippocampal contouring was manually generated on 3-dimensional magnetic resonance images according to the Radiation Therapy Oncology Group 0933 atlas. The distribution of metastases was assessed relative to the hippocampus: 0 to 5 mm for the first perihippocampal area and 5 to 15 mm for the rest of the perihippocampal area. RESULTS: The median patient age was 8.79 years (33% female). After a follow-up of 2.4 years, 43 patients were alive; 28 had had brain metastasis at diagnosis and 2 at relapse, with 16% in the first perihippocampal area and 43% in the rest of the perihippocampal area. Of the 18 patients without brain metastases at diagnosis, including M1 patients, none developed secondary lesions within the first or the rest of the perihippocampal area, after receiving 36 Gy. No clinical or biological factor was significantly associated with the development of perihippocampal metastases. CONCLUSIONS: Our results suggest the HA-WBI strategy should be evaluated for the subgroup of high-risk MB patients without metastatic disease.

Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation.

BACKGROUND: The purpose of GORTEC 2000-01 was to compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation. METHODS: Operable patients with untreated stage III or IV larynx or hypopharynx invasive squamous cell carcinoma who required total laryngectomy were randomly assigned to three cycles of induction chemotherapy with either TPF or PF, followed by radiation therapy for responders. The primary endpoint was three-year larynx preservation rate. Secondary endpoints included larynx dysfunction-free survival (LDFFS), overall survival (OS), disease-free survival (DFS), loco-regional control rate (LCR), cause of death, and later toxicity rates. Survival and other data were analyzed by Kaplan-Meier methods. All statistical tests were two-sided. RESULTS: Two hundred thirteen patients were treated with median follow-up of 105 months. The five- and 10-year larynx preservation rates were 74.0% (95% CI = 0.64 to 0.82) vs 58.1% (95% CI = 0.47 to 0.68) and 70.3% (95% CI = 0.58 to 0.8) vs 46.5% (95% CI = 0.31 to 0.63, P = .01) in the TPF vs PF arm, respectively. The five- and 10-year LDFFS rates were 67.2% (95% CI = 0.57 to 0.76) vs 46.5% (95% CI = 0.36 to 0.57) and 63.7% (95% CI = 0.52 to 0.74) vs 37.2% (95% CI = 0.24 to 0.52, P = .001), respectively. OS, DFS, and LCR were not statistically improved in the TPF vs the PF arm. Statistically fewer grade 3-4 late toxicities of the larynx occurred with the TPF regimen compared with the PF arm (9.3% vs 17.1%, G-test, P = .038). CONCLUSION: Long-term follow-up confirms that induction chemotherapy with TPF increased larynx preservation and larynx dysfunction-free survival. In this larynx preservation approach using induction chemotherapy, TPF should be recommended, followed by radiation therapy.

Feasibility of preoperative and postoperative chemoradiotherapy in gastric adenocarcinoma. Two phase II studies done in parallel. Fédération Francophone de Cancérologie Digestive 0308.

BACKGROUND: For resectable gastric cancer, both postoperative chemoradiotherapy and perioperative chemotherapy demonstrate high-level evidence for improved survival in Western populations. To evaluate the feasibility of pre- or postoperative chemoradiotherapy, we proposed two multicentre phase II studies. PATIENTS AND METHODS: Patients with localised, histologically confirmed gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status <2 judged suitable for curative resection were eligible. Eligible patients were assigned to either preoperative chemoradiotherapy followed by surgical resection or surgical resection followed by chemoradiotherapy depending on each centre. Chemoradiotherapy regimen included four courses of FOLFIRI (5 Fluorouracil, Leucovorin, Irinotecan) regimen then Concurrent fluorouracil at 200 mg/m2/d by continuous infusion 5 days each week. A dose of 50 Gy in 25 fractions in the preoperative study, or 45 Gy in 25 fractions in the postoperative study, was delivered. The primary end-point for both studies was the proportion of patients, who completed the therapeutic sequence. RESULTS: Between September 2007 and January 2010, 63 patients were included in both studies. The postoperative study was stopped for futility at the first step. In the preoperative study, 31 patients (73.8%, confidence interval (CI) 95%: 65.8-90.1%) received complete therapeutic sequence. Serum albumin and dietary restriction evaluated by QLQ-STO22 (Quality of Life-Stomach module) score were significantly linked with chemoradiotherapy feasibility in univariate analysis with respectively Odds-ratio (OR) 1.16 [CI 95%: 1.01-1.33] and 0.17 [0.03-0.89], p=0.04. Median overall survival time was 26.4 months in the preoperative study. CONCLUSION: Feasibility of chemoradiotherapy was not achieved for these studies: 73.8% (CI 95%: 65.8-90.1) and 42.9% (CI 95%: 21.8-66%) in preoperative and postoperative settings respectively.

[Multidisciplinary meetings in oncology do not impact the physician-patient relationship]. / La réunion de concertation pluridisciplinaire en cancérologie ne modifie pas la relation entre le médecin et son patient.

CONTEXT: The setting of multidisciplinary meeting (MDM) by the French Cancer Plan has introduced new decisional elements in the patient-physician relationship in oncology. METHODS: To assess the potential impact of MDM on this relationship, a study was conducted at the Tours Hospital: 145 questionnaires were collected from patients whose files have been discussed in MDM, 40 questionnaires were collected from physicians attending these meetings and an analysis of 324 files was performed. RESULTS: Patients recognize the decisional process of MDM as reassuring for 80% of them. However, a majority (73%) expressed that the most important for them is the relationship with the referring physician, almost all (96%) having a total or great confidence in him. The results emphasize that trust appears to be related to the quality of communication, open dialogue and the competence of the doctor in particular in the choice of treatment. A review of files shows that in 91% of cases, the opinion of the RCP is applied and that, in 69% of cases, the referring doctor delivers the information to the patient after MDM. From the physicians' perspective, 33/40 report that the MDM do not alter their relationship with the patient. We note that 35/40 express that the consultation after MDM facilitates the presentation of the decision and 37/40 that the decision is always or often applied in accordance with the opinion of the MDM. CONCLUSION: MDM appears in most cases in this study not to modify the patient-physician relationship. Due to the patient confidence into the referring physician, the role of this one is essential in integrating the decisional multidisciplinary opinion of MDM and it is important to ensure from his/her disengagement in the decisional process.

Concomitant chemoradiotherapy using carboplatin, tegafur-uracil and leucovorin for stage III and IV head-and-neck cancer: results of GORTEC Phase II study.

PURPOSE: Concomitant chemoradiotherapy is the standard treatment of locally advanced, nonresectable, head-and-neck squamous cell carcinoma. However, the optimal chemotherapy regimen is still controversial. The objective of this Phase II study was to evaluate the feasibility and efficacy of a concomitant treatment using tegafur-uracil, leucovorin, carboplatin, and radiotherapy. METHODS AND MATERIALS: A total of 77 patients with head-and-neck squamous cell carcinoma Stage III and IVA were enrolled between October 2003 and July 2005. Of the 77 patients, 72 were eligible. They were treated with tegafur-uracil (300 mg/m(2)/d) and leucovorin (75 mg/d) from Days 1 to 19 and from Days 29 to 47 and carboplatin (70 mg/m(2) intravenously for 4 consecutive days), in three cycles every 21 days. Conventional radiotherapy was delivered to a total dose of 70 Gy in 35 fractions. RESULTS: With a mean follow-up of 22.8 months, the 3-year locoregional control, overall survival and disease-free survival actuarial rate was 33.1%, 41.9%, and 27.2%, respectively. The compliance of the treatment was correct. The main acute toxicity was mucositis, with 62% Grade 3-4. Three patients (4.2%) died of acute toxicity. The incidence and severity of late toxicity was acceptable, with 32% Grade 3 and no Grade 4 toxicity. CONCLUSION: The protocol of concomitant chemoradiotherapy using tegafur-uracil, leucovorin, and carboplatin for locally advanced unresectable head-and-neck squamous cell carcinoma is feasible. The compliance was correct. The incidence and severity of the acute and late toxicities were acceptable, but not improved. The efficacy of this regimen seems equivalent to the main protocols of concurrent chemoradiotherapy. It represents a possible alternative for patients without an intravenous catheter.

Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation.

BACKGROUND: Chemotherapy with cisplatin (P) and 5-fluorouracil (F) followed by radiotherapy in patients who respond to chemotherapy is an alternative to total laryngectomy for patients with locally advanced larynx and hypopharynx cancer. Data suggest that docetaxel (T) may add to the efficacy of PF. The objective of this trial was to determine whether adding T to PF could increase the larynx preservation rate. METHODS: Patients who had larynx and hypopharynx cancer that required total laryngectomy were randomly assigned to receive three cycles of TPF or PF. Patients who responded to chemotherapy received radiotherapy with or without additional chemotherapy. Patients who did not respond to chemotherapy underwent total laryngectomy followed by radiotherapy with or without additional chemotherapy. The primary endpoint was 3-year larynx preservation rate. Secondary endpoints included acute toxicities and overall response. All statistical tests were two-sided. RESULTS: Baseline patient and tumor characteristics were well balanced between the TPF (n = 110) and PF (n = 103) groups. With a median follow-up of 36 months, the 3-year actuarial larynx preservation rate was 70.3% with TPF vs 57.5% with PF (difference = 12.8%; P = .03). Patients in the TPF group had more grade 2 alopecia, grade 4 neutropenia, and febrile neutropenia, whereas patients in the PF group had more grade 3 and 4 stomatitis, thrombocytopenia, and grade 4 creatinine elevation. The overall response was 80.0% in the TPF group vs 59.2% in the PF group (difference = 20.8%; P = .002). CONCLUSIONS: In patients with advanced larynx and hypopharynx carcinomas, TPF induction chemotherapy was superior to the PF regimen in terms of overall response rate. These results suggest that larynx preservation could be achieved for a higher proportion of patients.

Online quality control, hyperfractionated radiotherapy alone and reduced boost volume for standard risk medulloblastoma: long-term results of MSFOP 98.

PURPOSE: To determine event free and overall survival, and long-term cognitive sequelae of children with standard-risk medulloblastoma (SRM) treated with hyperfractionated radiotherapy, conformal reduced boost volume without chemotherapy, and online quality assurance. PATIENTS AND METHODS: Forty-eight patients (age 5 to 18 years) were included in the Medulloblastoma-Société Française d'Oncologie Pédiatrique (MSFOP 98) protocol (December 1998 to October 2001). Patients received hyperfractionated radiotherapy (HFRT; 36 Gy, 1 Gy/fraction twice per day) to the craniospinal axis followed by a boost to the tumor bed (1.5-cm margin) to a dose of 68 Gy. Records of craniospinal irradiation were reviewed before treatment started. Neuropsychologic evaluations were done according to the protocol (1, 3, 5, and 7 years after irradiation). Cognitive outcomes were followed longitudinally with full-scale intelligence quotient (FSIQ) obtained with age-adapted Wechsler scales. RESULTS: After a median follow-up of 77.7 months, 6-year overall survival (OS) and event-free survival (EFS) rates for the cohort were 78% (95% CI, 66% to 90%) and 75%, respectively (95% CI, 62% to 87%). Thanks to quality control, 14 major deviations were detected. Annual full scale IQ decline was 2 points over a 6-year period. Predicted change in FSIQ points per year was 2.15 (95% CI, -1.24 to 3.51) with an intercept (ie, predicted FSIQ) of 93.57 at baseline. CONCLUSION: HFRT protocol with conformal reduced boost and online quality control allows excellent long-term OS and EFS in the absence of chemotherapy. In addition, FSIQ drops seem to be less pronounced than previously reported with standard irradiation regimens.