Stereotactic body radiation therapy for adrenal gland metastases: A multi-institutional outcome analysis.

Aim: The adrenal gland is a common site of metastasis with a rate of up to 27% in autopsy series. The incidence of these metastases is increasing due to greater use of Positron Emission Tomography scans and improved overall survival of patients with metastatic cancers. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment option for metastasis. The aim of this study is to assess prognostic factors influencing local control, progression-free and overall survival in oligometastatic patients treated with SBRT for an adrenal metastasis. Methods: In this multicentric retrospective study, we included patients with adrenal metastases treated with SBRT between 2010 and 2021 in eleven french centers. All primary tumors were included. Results: A total of 110 patients treated for 121 adrenal lesions were included. Non-small-cell lung cancer was the predominant histologic type (55.4 %). Eighty-two percent of patients had at least 2 metastatic sites. The median Planning Target Volume was 70 cm3 with a median prescription dose of 40 Gray (Gy). The mean Biologically Effective Dose (BED) 10 dose was 74.2 Gy. Local control at 1 and 2 years was 85.9 % and 72.5 % respectively. The median overall survival and progression-free survival were 31.6 and 8.5 months respectively. Local control was significantly improved by systemic treatment one month before or after SBRT (p = 0.009) and by a BED10 greater than or equal to 50 Gy (p = 0.003).In multivariate analysis, oligometastatic presentation (p = 0.009) and a metachronous metastatic presentation (p = 0.008) were independent factors for progression-free survival.Tolerance was excellent, no grade 3 and 4 toxicities were described due to SBRT. Conclusion: Stereotactic radiotherapy of adrenal metastases makes possible a local control of more than 85% at one year and was well tolerated. The factors influencing survival in oligometastatic patients still need to be found in order to better select those who benefit the most from this type of treatment.

Stereotactic body radiotherapy for mediastinal lymph node with CyberKnife®: Efficacy and toxicity.

PUPRPOSE: Stereotactic body radiotherapy is more and more used for treatment of oligometastatic mediastinal lymph nodes. The objective of this single-centre study was to evaluate its efficacy in patients with either a locoregional recurrence of a pulmonary or oesophageal cancer or with distant metastases of extrathoracic tumours. PATIENTS AND METHODS: Patients with oligometastatic mediastinal lymph nodes treated with CyberKnife from June 2010 to September 2020 were screened. The primary endpoint was to assess local progression free survival and induced toxicity. Secondary endpoints were overall survival and progression free survival. The delay before introduction of systemic treatment in the subgroup of patients who did not receive systemic therapy for previous progression was also evaluated. RESULTS: Fifty patients were included: 15 with a locoregional progression of a thoracic primary tumour (87% pulmonary) and 35 with mediastinal metastasis of especially renal tumour (29%). Median follow-up was 27 months (6-110 months). Local progression free survival at 6, 12 and 18 months was respectively 94, 88 and 72%. The rate of local progression was significantly lower in patients who received 36Gy in six fractions (66% of the cohort) versus other treatment schemes. Two grade 1 acute oesophagitis and one late grade 2 pulmonary fibrosis were described. Overall survival at 12, 18 and 24 months was respectively 94, 85 and 82%. Median progression free survival was 13 months. Twenty-one patients were treated by stereotactic body irradiation alone without previous history of systemic treatment. Among this subgroup, 11 patients (52%) received a systemic treatment following stereotactic body radiotherapy with a median introduction time of 17 months (5-52 months) and 24% did not progress. CONCLUSION: Stereotactic body irradiation as treatment of oligometastatic mediastinal lymph nodes is a well-tolerated targeted irradiation that leads to a high control rate and delay the introduction of systemic therapy in selected patients.

[French careers in oncology radiotherapy: Crossing views]. / Carrières en oncologie radiothérapie : réflexions croisées SFjRO-SFRO-SNRO.

The French Society of Young Radiation Oncologists (SFjRO), the National Union of Radiation Oncologists (SNRO) and the French Society of Oncological Radiotherapy (SFRO) aim to reconcile career opportunities and demographic needs in oncology. In 2021, 932 radiation oncologists (RO) are in regular activity in France, this represents an increase of more than 20% in ten years. Physician distribution is changing in public hospitals, cancer centers and private clinics. Currently one third of ROs works in each sector. In addition, fifteen percent of ROs have a mixed activity. In 2021, 180 young RO (trainees and residents) were questioned by SFjRO board about their training, internship, coaching and career guidance. An interactive communication was organized during the 32nd SFRO Meeting in 2021. It was an opportunity to bring the results of this study. More than 70% RO interviewed answered to the survey, for 55% among them, career choice was difficult. In order to help young ROs in their professional approach, three RO made an oral presentation during this session, about radiotherapy in public hospitals, private centers or with a mixed practice. The aim of this article is to summarize the highlights of the last SFjRO/SFRO session: expectations of young RO, career prospects and trends.

Herpes encephalitis during natalizumab treatment in multiple sclerosis.

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

[Stereotactic body radiation therapy for hepatocellular carcinoma: Results from a retrospective multicentre study]. / Radiothérapie en conditions stéréotaxiques du carcinome hépatocellulaire : résultats d'une étude rétrospective multicentrique.

PURPOSE: The purpose of this paper was to describe local control, overall survival, progression-free survival and toxicity of CyberKnife®-based stereotactic body radiation therapy of hepatocellular carcinoma. MATERIAL AND METHODS: Records of all the patients treated for hepatocellular carcinoma at the Eugene-Marquis cancer centre, Rennes and the Bretonneau hospital, Tours (France), between November 2010 and December 2016, were reviewed. Radiation therapy was performed as a salvage treatment, while awaiting liver transplantation or if no other treatment was possible. RESULTS: One hundred and thirty-six patients were consecutively included in the study. The median follow-up was 13months. Median total dose prescribed, fractionation and overall treatment time were respectively 45Gy, three fractions and 5 days. Overall survival, progression-free survival and local control rates at 1year and 2years were 79.8 % and 63.5 %, 61.3 % and 39.4 %; 94.5 % and 91 %. Two grade 3 acute toxicity events and two grade 4 late toxicity events corresponding to a duodenal ulcer have been reported. Seven patients underwent classic radiation-induced hepatitis and 13 patients showed non-classical radiation-induced hepatitis. Barcelona Clinic Liver Cancer stage, World Health Organisation grade and planning target volume were correlated with overall survival in univariate Cox analysis. CONCLUSION: Stereotactic body radiation therapy is effective and well-tolerated for inoperable hepatocellular carcinoma or as a bridge to liver transplantation. Toxicity is mainly related to cirrhotic background and requires a selection of patients and strict dose constraints.

[Documentation management: from theory to practice]. / La gestion documentaire: de la théorie à la pratique.

The management of the documentation is one of the key points regarding the efficacy and the performance of the quality management of health centres. It offers to all professionals the possibility to be informed on the procedures in use, leading to a pool of documents for improvement of organisations and for securing the critical steps of the patient management. In this paper, we will describe the optimal organisation of the documentation according to Haute autorité de santé (HAS) and ISO recommendations, then we will discuss in concrete terms the potential methods usable for the production of a tool well adapted to our routine practice, in order to achieve the objectives for security.

Reirradiation of gliomas under stereotactic conditions: Prognostic factors for survival without relapse or side effects, a retrospective study at Tours regional university hospital (France).

PURPOSE: To search for factors correlated with relapse-free survival following stereotactic reirradiation in patients with recurrent glioma following radiochemotherapy and evaluate tolerance to this treatment. PATIENTS AND METHODS: Initial radiotherapy was given according to the protocol of Stupp and al. Reirradiation was performed using the CyberKnife® system. Patients could have had surgical resection initially and at the time of recurrence. We analysed 13 patients treated between July 2010 and September 2014. The median age was 55 years. The doses delivered ranged from 20 to 36Gy, in one to ten fractions. RESULTS: Median survival after stereotactic radiotherapy was 14 months. Survival without relapse was 3.7 months. Factors significantly influencing duration of relapse-free survival were: age (P=0.04), total dose (P=0.02), dose per fraction (P=0.04) and number of fractions (P=0.01). We found no correlation between gross tumour volume, clinical target volume, grade of tumour or prescription isodose and relapse-free survival following radiochemotherapy. Three patients developed radionecrosis. CONCLUSION: Reirradiation under stereotactic conditions is well tolerated. A dose of more than 30Gy delivered in 5 or more fractions seems to prolong relapse-free survival.

A large French multicenter retrospective series of T1-T2N0 vocal cords carcinomas treated with exclusive irradiation.

PURPOSE: The main objective of this study was to evaluate the 5-year efficacy of exclusive laryngeal radiotherapy without node prophylactic irradiation for localized cancers of the vocal cords. PATIENTS AND METHODS: We retrospectively reviewed charts from 258 patients with T1-T2N0 glottic carcinoma irradiated from April 1987 to March 2015 in four France western centers, including pretreated patients. Toxicity was analyzed according to CTCAE v4.0 classification. RESULTS: The median follow-up was 50 months. The median age was 67 years with 87% men and 85.5% had T1 tumor. Five years overall survival was 77.5% (95% confidence interval [95% CI]: 71.4-83.5), 5 years local control was 86.8% (95% CI: 82.3-91.3), specific survival rate was 95% (95% CI: 92.2-97.9) and final laryngectomy-free survival was 87.5% (95% CI: 82.2-92.9). Most toxicities were grade 1 and 2. Grade 3 acute toxicity was 15.5% for the radiation laryngitis, 3.5% for radiodermatitis and 7.7% for dysphonia. Grade 3 chronic toxicity was 3.5% for dysphonia and there were two cases of tracheal stenosis treated by tracheotomy. CONCLUSION: Radiotherapy provides good results in local control of stage I and II vocal cords cancers as well as the toxicity level.

Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma.

BACKGROUND: We designed a randomized clinical trial to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV (i.e., advanced oropharynx carcinoma). METHODS: A total of 226 patients have been entered in a phase III multicenter, randomized trial comparing radiotherapy alone (arm A) with radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B, patients received during the period of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuous infusion. The two arms were equally balanced with regard to age, sex, stage, performance status, histology, and primary tumor site. RESULTS: Radiotherapy compliance was similar in the two arms with respect to total dose, treatment duration, and treatment interruption. The rate of grades 3 and 4 mucositis was statistically significantly higher in arm B (71%; 95% confidence interval [CI] = 54%-85%) than in arm A (39%; 95% CI = 29%-56%). Skin toxicity was not different between the two arms. Hematologic toxicity was higher in arm B as measured by neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were, respectively, 51% (95% CI = 39%-68%) versus 31% (95% CI = 18%-49%) and 42% (95% CI = 30%-57%) versus 20% (95% CI = 10%-33%) for patients treated with combined modality versus radiation therapy alone (P =.02 and.04, respectively). The locoregional control rate was improved in arm B (66%; 95% CI = 51%-78%) versus arm A (42%; 95% CI = 31%-56%). CONCLUSION: The statistically significant improvement in overall survival that was obtained supports the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.

[Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery enhances late toxicities]. / La chimiothérapie concomitante de la radiothérapie augmente la toxicité tardive après chirurgie conservatrice du cancer du sein.

PURPOSE: In 1996, a multicenter randomized study comparing after breast-conservative surgery, sequential vs concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen patients were included in this trial. After a median follow-up of 6.7 (4.3-9) years, we decided to prospectively evaluate the late effects of these two strategies. PATIENTS AND METHODS: A total of 297 patients were asked to follow-up from the five larger including institutions. Seventy-two percent (214 patients) were eligible for late toxicity. After breast-conserving surgery with axillary dissection, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with RT (arm B). In all patients, CT regimen combined mitoxantrone (12 mg/m(2)), 5-FU (500 mg/m(2)), and cyclophosphamide (500 mg/m(2)), 6 cycles (day 1-day 21). In arm B, patients received concurrently the first 3 cycles of CT with RT. In arm A, RT started 3 to 5 weeks after the 6th cycle of CT. Conventional RT was delivered to the whole breast using a 2 Gy-fraction protocol to a total dose of 50 Gy (+/-boost to the primary tumour bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist according to the LENT-SOMA scale. Skin pigmentation was also evaluated using a personal 5-points scoring system (excellent, good, moderate, poor, very poor). RESULTS: Among the 214 evaluated patients, 107 were treated in each arm. The two populations were homogeneous for patients', tumors' and treatment characteristics. Subcutaneous fibrosis (SF), telengectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Twenty patients experienced grade superior or equal to 2 (SF) in arm B vs five in arm A (P=0.003). Twenty-five and seven patients showed grade superior or equal to 2 (T) in arm B and A, respectively (P=0.001). Forty-four and twenty patients showed grade superior or equal to 2 (BA) in arm B and A, respectively (P=0.0006). Thirty patients experienced grade superior or equal to 3 (SP) in arm B vs fifteen in arm A (P=0.02). No statistical difference was observed between the two arms concerning grade superior or equal to 2 pain, breast oedema, and lymphoedema. No deaths were caused by late toxicity. CONCLUSION: Following breast conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects.

Stereotactic body re-irradiation therapy for locally recurrent prostate cancer after external-beam radiation therapy: Initial report.

PURPOSE: Management of prostate cancer relapses after external-beam radiation therapy is still undefined. Re-irradiation schedules have been explored in different tumour sites. In this report, we present our preliminary experience of re-irradiation using stereotactic body radiotherapy for localized prostate cancer failure. MATERIAL AND METHODS: Between March 2011 and October 2014, robotic stereotactic body radiation therapy was administered to patients previously treated with external-beam radiation therapy to a median dose of 71.1Gy (range, 45-76.5Gy) and with biochemical failure corresponding to a local in-field recurrence of prostate cancer. Ten patients had recurrences after postoperative external-beam radiotherapy. Patients underwent a pelvic MRI to confirm the recurrence and a total body staging using a ((18)F)-fluorocholine PET/CT. The prescription dose consisted of five fractions of 7.25Gy to a total dose of 36.25Gy. Efficacy was evaluated based on biochemical response and toxicity was evaluated according to CTCAE v.4.0 questionnaires and International Prostate Symptom Score. RESULTS: Twenty-one patients were treated and followed for a median time of 11.7 months (mean: 13.4 months; range: 2.5-46.5 months). Median time between the first external-beam radiation therapy of prostate cancer and the first day of CyberKnife(®) treatment was 111 months (range: 38-398 months). One-year biochemical recurrence-free survival rate was 83.3%, and only one in-field progression was reported. Two patients had a biochemical failure corresponding to metastatic progression without evidence of local recurrence. Treatment was well tolerated, with only one grade 2 acute genitourinary toxicity, no grade≥2 acute gastrointestinal or late toxicities were reported. CONCLUSION: Stereotactic body re-irradiation therapy using CyberKnife(®) after failed external-beam radiation therapy showed favourable results in terms of in-field local and biochemical control. Toxicity was low and acceptable. Further prospective studies are needed to confirm these results to select patient and to evaluate the introduction of androgen-deprivation therapy.

[Radiotherapy of hypopharynx cancers]. / Radiothérapie des cancers de l'hypopharynx.

The intensity-modulated radiotherapy is the gold standard in the treatment of hypopharynx cancers. Early T1 and T2 tumours could be treated by exclusive radiotherapy or surgery. For tumours requiring total pharyngolaryngectomy (T2 or T3), induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy are possible. For T4 tumours, surgery must be proposed. The treatment of lymph nodes is based on the initial treatment of the primary tumour. In non-surgical procedure, in case of sequential radiotherapy, curative dose is 70Gy and prophylactic dose is 50Gy. An integrated simultaneous boost radiotherapy is allowed (70Gy in 2Gy per fraction and 56Gy in 1.8Gy per fraction or 70Gy in 2.12Gy per fraction). Postoperatively, radiotherapy is used for locally advanced cancers with dose levels based on pathologic criteria (66Gy for R1 resection, 50 to 54Gy for complete resection). Volume delineation is based on guidelines.

[Radiotherapy of larynx cancers]. / Radiothérapie des cancers du larynx.

Intensity-modulated radiotherapy is the gold standard in the treatment of larynx cancers (except T1 glottic tumour). Early T1 and T2 tumours may be treated by exclusive radiation or surgery. For tumours requiring total laryngectomy (T2 or T3), induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy is possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on the initial treatment of the primary tumour. In non-surgical procedure, in case of sequential radiotherapy, the curative dose is 70Gy and the prophylactic dose is 50Gy. An integrated simultaneous boost radiotherapy is allowed (70Gy in 2Gy per fraction and 56Gy in 1.8Gy per fraction or 70Gy in 2.12Gy per fraction). Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria (66Gy for R1 resection, 50 to 54Gy for complete resection). Volume delineation was based on guidelines.

[Larynx preservation, state of the art]. / La préservation laryngée, état de la question.

Larynx preservation in advanced pharyngolaryngeal cancers has been a major challenge in clinical research over the past two decades. Subtotal surgery (endoscopic laser surgery, supracricoid partial laryngectomies and hemilaryngopharyngectomies) has allowed reducing the indications of the so-called "mutilating" surgery. On the other hand, the modification of fractionation has notably improved the results of definitive irradiation (but most probably for supraglottic tumors). The main clinical research has been carried out with either sequential or concurrent chemo-irradiation. Induction chemotherapy followed by irradiation in good responders or by surgery in poor responders allowed to preserve the larynx in around half the cases without deleterious impact on overall survival. Concurrent chemo-irradiation trials suggested that the larynx preservation rates could be increased but overall survival remained unchanged and mucositis was a notable side effect. The next step could be the combination of induction chemotherapy followed by concurrent chemo-irradiation in good responders. Finally, the place of new drugs (taxanes, targeted therapies) is to be explored in this context.

[Propositions for the selection and the delineation of peritumoral microscopic disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)]. / Proposition de sélection et délimitation des volumes cibles microscopiques péritumoraux dans les cancers de la cavité buccale et de l'oropharynx (aires ganglionnaires exclues).

This article reviews the concept of selectivity in peritumoral microscopic disease to be included in the Clinical Target Volume (CTV) for elective treatment for oral cavity and oropharyngeal squamous cell carcinoma, using the local tumoral spread. The objective of the present article is to present a procedure for the delineation of the target volumes, required for an appropriate application of 3-DCRT and IMRT for head and neck cancers. These propositions are for the delineation of microscopic peritumoral target volumes when external beam irradiation is required. CTVs are illustrated on CT sections.

[Long-term outcome of neoadjuvant radiochemotherapy followed by surgery for esophageal cancer: a single institution retrospective study of 102 patients]. / Résultats à long terme de la chimioradiothérapie néoadjuvante des cancers de l'œsophage: étude rétrospective monocentrique sur 102 patients.

PURPOSE AND OBJECTIVES: To report survival and morbidity of a large homogeneous cohort of patients with a locally advanced esophageal or cardia carcinoma and put in evidence predictive factors of locoregional control and survival. PATIENTS AND METHODS: Hundred and two patients were treated at the university hospital of Tours between 1990 and 2010 and received neo-adjuvant chemoradiation therapy with external irradiation (40Gy-44Gy) and two courses of chemotherapy (5-fluoro-uracile and cisplatine). Esophagectomy associated with lymph node dissection was performed about ten weeks after the end of chemoradiation therapy. RESULTS: The median follow-up was 22.4 months [6-185 months]. The overall survival rates at 2 and 5years were 53% and 27%, respectively. The median overall survival was estimated at 27months. The overall 2-year survival between patients "responders" and patients "non-responders" was 67% vs 26%, respectively (P<0.0001). In case of histological response, there was a benefit in terms of overall survival (P<0.0001), locoregional control (P<0.0036) and disease-free survival (P<0.001). Overall survival at 2years was 64% for ypN0 group vs 32% for ypN1 group (P<0.0001). The median survival was estimated at 37months against 15months in the absence of lymph node involvement (P<0.0001). CONCLUSION: Our results in terms of survival, tolerance and morbidity and mortality were comparable to those in the literature. Complete histological response of lymph node was associated with an improvement of local control, disease-free survival and overall survival.

Enhanced acute toxicity in oropharynx carcinoma treated with radiotherapy and concomitant cisplatin, 5-fluorouracil and mitomycin C.

The aim of this study was to establish the feasibility of giving concomitant radiotherapy and 3 cycles of chemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced inoperable oropharyngeal cancer. From March 1990 to September 1993, 27 male patients (mean age 55 years) were included in this study. 3 patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). All patients received conventional radiotherapy delivering 70 Gy in 35 fractions and 52 days, and three cycles of chemotherapy starting on day 1, 21 and 42 with CDDP 20 mg/m2 and 5-FU 400 mg/m2 day 1 to day 4, and MMC 10 mg/m2 day 1. With a mean follow-up of 34 months (17-59), 10 patients (37%) were alive and free of disease. Among the 17 other patients, 8 died of cancer. Crude locoregional control rate was 78%, and probability of local control at 1 and 2 years was 85 and 80%, respectively. One- and 2-year survival rates were 48 and 31%, respectively, for both overall and disease-free survival. Grade 3 or 4 mucositis occurred in 22 patients (81%); enteral feeding was necessary for 63%; mean weight loss was 5.7 kg. Grade > 2 thrombocytopenia occurred in 11 patients (41%), grade > 2 neutropenia in 8 patients (29%), grade > 2 anaemia in 4 patients (15%). Febrile neutropenia or aplasia occurred in 5 patients (19%). 2 patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 1 month after treatment with grade 4 thrombocytopenia and septicaemia. In conclusion, a high complete response rate has been achieved with this concomitant chemo- and radiotherapy, but with severe digestive and haematological toxicity. Addition of MMC to 5-FU and CDDP might have been responsible for this increased toxicity. This therapeutic combination is therefore not routinely feasible.

Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group.

The European Organisation for Research and Treatment of Cancer (EORTC) 22921 four-arm randomised trial questioned the value of preoperative chemoradiation (XRT-CT) versus preoperative radiation (XRT) and the value of additional postoperative chemotherapy (CT) versus none in T3-T4 M0 resectable rectal cancer patients. We report on the preoperative toxicity, treatment compliance and early deaths (all deaths up to 30 days after surgery) of the two treatment modalities in patients who were entered into trial before January 2001. In the XRT Group (group A), patients received 45 Gy, 25 fractions over 5 weeks. In the XRT-CT Group (group B), two 5-day courses of CT were added to the first and fifth weeks of XRT. For each CT course: 5-fluorouracil (5-FU) 350 mg/m2/day and Leucovorin (LV) 20 mg/m2/day were given. 398 and 400 patients started treatment in groups A and B, respectively. Grade 2+acute diarrhoea occurred in 17.3 and 34.3% of patients in groups A and B, respectively (P<0.005). The other side-effects remained unchanged or were only marginally increased. The compliance with RT was 98.5 and 95.5% in groups A and B, respectively. In group B, 78.7 and 71.1% of the patients received 95-105% of the planned CT doses at the first and second courses, respectively. 6 patients died preoperatively, 2 from toxicity in group B. 8 patients (1%) died within the 30 days after surgery in both groups. At the doses recommended in the protocol, the addition of 5-FU-LV to preoperative XRT slightly increased the amount of acute toxicity. However, the compliance with the radiation protocol or the feasibility of surgery did not decrease.

Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.

This comparative phase III trial of mitoxantrone+vinorelbine (MV) versus 5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improved tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC, 142 received MV). Patient characteristics were matched in each arm and stratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in the two arms (33.3% for FAC/FEC versus 34.5% for MV), but MV was more effective in patients who had received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20-47) for MV P=0.025) with a better progression-free survival (PFS) (5 months (range 1-18 months) versus 8 months (range 1-27 months); P=0.0007 for FAC/FEC versus MV, respectively) while FAC/FEC was more effective in previously untreated patients (ORR 43% (95% CI 33-53) versus 35% (95% CI 25-45), P=0.26; PFS 9 months (range 0-29 months) versus 6 months (range 0-26 months) P=0.014). Toxicity was monitored through the initial six cycles of therapy; febrile neutropenia and delayed haematological recovery was more frequent for MV (P=0.001), while nausea/vomiting of grades 3-4 was greater for FAC/FEC (P=0.031), as was alopecia (P=0.0001), cardiotoxicity was the same for the two regimens. MV represents a chemotherapy combination with equivalent efficacy to standard FAC/FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematological suppression and risk of febrile neutropenia with MV compared with a higher risk of subjectively unpleasant side-effects such as nausea/vomiting and alopecia with FAC/FEC.

Concomitant radiochemotherapy or accelerated radiotherapy: analysis of two randomized trials of the French Head and Neck Cancer Group (GORTEC).

In the early 1990s, when conventional radiotherapy (RT) was the standard of care in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), two main options were being tested to improve the efficacy and the therapeutic ratio of RT. The first approach evaluated the effect of adding chemotherapy (CT) simultaneously to RT (RT-CT), while the second approach assessed the effect of modified fractionated RT. To answer these two questions, in 1994, the French Group for Head and Neck Oncology Radiotherapy (GORTEC) initiated two randomized trials. A total of 494 patients were entered in these two parallel phase III multicenter trials comparing conventional RT (70 Gy in 35 fractions) either with concomitant RT-CT (226 patients; 70 Gy in 35 fractions with three cycles of a 4-day regimen comprising carboplatin and 5-fluorouracil [5FU]) or with very accelerated RT (268 patients) delivering 64 Gy in 3 weeks. The 5-year overall survival (OS), specific disease-free survival (DFS), and local-regional control rates were improved in favor of simultaneous RT-CT, whereas local-regional control was significantly improved with accelerated RT, along with a marginal effect on OS and DFS. This increased antitumor efficacy was in both cases associated with a marked increase in acute RT-induced toxicity, which was more pronounced with accelerated RT, whereas late effects were marginally increased with the addition of CT and not influenced by accelerated RT. We conclude that both concomitant RT-CT and accelerated RT improved tumor control rates, as compared to conventional RT, along with increased but manageable toxicity. The two regimens are currently being tested in an ongoing randomized study and also being compared to moderately accelerated RT and concomitant CT.