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Purpose: Low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy are known to be effective in the treatment of lip carcinomas. The aim of this study was to retrospectively compare oncologic and toxicity outcomes between the two techniques., Patients and Methods: From 2007 to 2018, patients at the Institut de cancérologie de Lorraine (France) who received exclusive or adjuvant interstitial brachytherapy for lip squamous carcinomas were studied. Two groups were defined: the LDR/PDR group, including patients treated with iridium-192 wires, or pulsed-dose rate technique, and the high-dose-rate group, with patients treated by high-dose-rate technique. The dose ranged between 50Gy and 65Gy (depending on previous surgery) for low-dose-/pulsed-dose rate treatments, and 39Gy for high-dose-rate (twice a day). Early, late toxicity events and oncologic control were reported., Results: Among the 61 patients whose data were analyzed retrospectively, 36 received the low-dose-/pulsed-dose rate treatment (59%) and 25 the high-dose-rate brachytherapy (41%). The median follow-up time was 44 months. At 36 months, the local control rates were 96.3% for LDR/PDR group and 100% for HDR (P=0.180). The regional control rates were 85.9% and 92% without any difference according to the two groups (P=0.179). The specific overall survival rate was 95.5% with no difference between groups. There were more grade 2 or higher mucositis in the HDR group than in LDR/PDR group (40% versus 16.7%, P=0.042). One case of grade 3 mucositis was recorded in each group. No grade 3 late complications were recorded. High-dose-rate brachytherapy reduced the length of hospitalization by 2 days (P<0.001)., Conclusion: High-dose- or low-dose-/pulsed-dose rate brachytherapy seemed to be as effective and well tolerated in our experience of 61 patients., (Copyright © 2023. Published by Elsevier Masson SAS.)

Purpose: Skin squamous cells carcinomas (SCC) are frequently tumor, especially in the elderly population. Surgical excision is the standard treatment. But for patients suffering large tumor or/with comorbidity, a conservative approach with irradiation can be proposed. The hypofractionated schedule is used to shorten the overall treatment time with same results and without compromising therapeutic outcomes. The aim of this study is to assess the efficacy and tolerance of hypofractionated radiotherapy for invasive SCC of the scalp in elderly., Patients and Methods: We included patients suffering from SCC of the scalp and treated by hypofractionated radiotherapy at the Institut de cancérologie de Lorraine or centre Émile-Durkeim d'Épinal, from January 2019 to December 2021. Characteristics of patients, size of the lesion and side effects were collected retrospectively. Tumor size at 6 months corresponded to the primary endpoint. Toxicity was collected for the secondary endpoint., Results: Twelve patients with a median age of 85 years old were included. The mean size was 4,5cm with a bone invasion in 2/3 of cases. Radiotherapy was delivered after surgical excision for half of the patient. The dose delivered was 54Gy in 18 daily fractions size. Six months after irradiation: 6/11 patients had no residual lesion, 2/11 had a partial response with a residual lesion of about 1cm. 3 patients presented local recurrence. One patient died within 6 months of radiotherapy because of another comorbidity. In total, 25% had presented a grade 3 acute radiation dermatitis, no grade 4 toxicity., Conclusion: Short term of moderately hypofractionated schedule radiotherapy was a success with complete or partial response for more than 70% of the patients in squamous cell carcinomas. There is no major side effect., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients., Methods: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed., Results: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group., Conclusion: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Primary vaginal cancers are rare tumours, for which external beam radiotherapy and brachytherapy are major treatment tools. Given the complexity of brachytherapy techniques, the treatment should be performed in specialised centres. We present the recommendations of the French society for radiation oncology on the indications and techniques for external beam radiotherapy and brachytherapy for primary vaginal cancer., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

We present the update of the recommendations of the French society for radiation oncology on external radiotherapy and brachytherapy of anal canal carcinoma. The following guidelines are presented: indications, treatment procedure, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16 ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16 ink4a status, cTNM classification as well as both CD3 + and CD4 + T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.

Purpose: The ongoing phase 2/3 PRODIGE 26/CONCORDE trial compares chemoradiation therapy with and without dose escalation in patients with locally advanced or unresectable esophageal cancer. The results of a benchmark case procedure are reported here to evaluate the protocol compliance of participating centers as part of quality assurance for radiation therapy., Methods and Materials: Volume delineation, target coverage, and dose constraints to the organs at risk (OARs) were assessed on treatment plans of a common benchmark case performed by each participating center. The centers were classified in 3 categories: per protocol, minor acceptable deviation (MiD), or major unacceptable deviation (MaD). A plan was rejected if ≥4 MiDs or 1 MaD were found., Results: Thirty-5 centers submitted 43 plans. Among them, 14 (32.6%) were per protocol, 19 (44.2%) presented at least 1 MiD, 2 (4.6%) presented at least 1 MaD, and 8 (18.6%) presented both MiD and MaD. Overall, 11 (25.6%) plans were rejected. Only 1 plan was rejected because gross tumor volume was not correctly delineated. The OAR delineation was respected in all cases. Dose constraints to the OARs were respected in the majority of cases except for the heart, where one-third of the plans presented a deviation. As for the target volume, 3 plans (5.8%) had a major underdosage and 1 plan (1.9%) had a major overdosage. Overall, 58% of all treatments were planned with intensity modulated radiation therapy, whereas 42% were planned with 3-dimensional chemoradiation therapy. Significantly more plans in the intensity modulated radiation therapy group were accepted compared with the 3-dimensional chemoradiation therapy group (P = .03)., Conclusion: The high frequency of protocol deviations underlines the importance of a quality assurance program in clinical trials. Further work should assess the impact of quality assurance for radiation therapy on patient outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The conservative treatment of squamous cell carcinoma of anal canal by irradiation is recommended as first indication. Despite its rarity, significant improvements were obtained by retrospective or prospective clinical studies these 20 past years, evaluating concomitant chemotherapy and IMRT. Nevertheless, the individualisation of the treatment, over dose distribution, has poor data available. Fractionation remains classic (1.8-2.0Gy/Fr), but the optimal dose level remains under discussion. The strategy concerning the volumes and doses for the prophylactic volumes remains under discussion. This paper will describe the data published, and the recommendations of working Groups, and the main options under evaluation. To conclude, today only the absence of gap is recommended, the benefit of a one-step schedule reducing the treatment time, then increasing local control and survival, but personalised schedules remain under investigation., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: In clinical oncology, only a few applications have been developed using HPV as a personalized tumor marker, a lack most probably related to the limited information obtained by the classical Polymerase Chain Reaction (PCR) approach. To overcome this limitation, we have recently developed the capture-based Next-Generation Sequencing (NGS) "CaptHPV" assay, designed to provide an extensive and comprehensive molecular characterization of HPV DNA sequences associated with neoplasias, ie the sequence of the viral genome (245 genotypes), its physical state, viral load, integration site and genomic alterations at integration locus. These data correspond to highly specific tumor markers that can be used to improve diagnosis and patient's follow-up., Case Presentation: We report here a case that is a straightforward and practical illustration of the power of the CaptHPV method. A patient developed successively a carcinoma of the anal canal and of the tongue. The two tumors were squamous cell carcinoma, found associated with HPV16 using PCR. In order to document a possible metastasis to the tongue from the anal cancer, we performed CaptHPV analysis on the two tumors. The analysis of the anal carcinoma found 55 viral/human hybrid reads allowing the identification of the HPV16 DNA integration in the 4q25 chromosomal band locus with a 178,808 bp deletion in the cell genome. Molecular analysis of the tongue tumor disclosed 6110 reads of HPV16, with a viral pattern strictly identical to that of the anal tumor. A total of 131 hybrid reads between HPV16 and the cell genome were found, corresponding exactly to the same locus of integration of viral DNA at the 4q25 site. The 178,808 bp genomic deletion was also found in the lingual tumor. The exact identity of HPV insertional signatures in the two tumors, demonstrates unambiguously that the tongue tumor derived from the anal cancer whereas neither histological immunophenotyping nor classical viral analysis using PCR could allow a definitive diagnosis., Conclusion: Our observation indicates that the establishment of a detailed cartography of HPV DNA sequences in a tumor specimen provides crucial information for the design of specific biomarkers that can be used for diagnostic, prognostic or predictive purposes.

Background and Purpose: Intensity-modulated radiation therapy (IMRT) is currently indicated to treat anal squamous cell carcinoma (ASCC). Conformal dose delivery and steep dose gradients may cause marginal misses. We analyzed patterns of locoregional recurrences (LRR) and delineation quality to determine IMRT-specific predictive factors., Material and Methods: Lymph node area delineation was classified as "compliant" or "non-compliant" according to experts' workgroup recommendations. The recurrence volume (V recur ) was delineated on initial planning-CT by recurrence imaging registration. The V recur was determined to be "in-field" (IF), "marginal" (ML), or "out-of-field" (OF) in regard to the 95% isodose coverage., Results: Out of 165 patients, 30 had LRR. Among the 27 local recurrences (LR), 20 (74%) were IF, 4 (15%) ML, and 2 (7%) OF. Fourteen patients had regional recurrence (RR), amounted to 33 separate recurrence sites (RS). RS were mostly localized in inguinal (n = 12;36,4%), external iliac (n = 7;21.1%), presacral (n = 4;12.1%) and common iliac (n = 3;9.1%) nodes. Eighteen (54.5%) RS were IF, 6 (18.2%) ML, and 9 (27.3%) OF. Performance status ≥2 (p = 0.007) and active smoking (p = 0.025) were predictors of LR. Immunodepression (p = 0.012), external iliac involvement (p < 0.001), and non-compliant delineation for ≥10 areas (p = 0.005) were predictors of RR., Conclusions: New predictive factors for recurrences of ASSC treated with IMRT have been found, suggesting that the delineation accuracy is essential for regional control., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: To carry out a prognosis study of the prospective studies KANAL 2 and ACCORD 03 in order to highlight new prognostic factors of colostomy-free survival in patients with locally advanced anal canal carcinoma., Patients and Methods: KANAL 2 and ACCORD 03 were phase 2 and phase 3 multicenter trials with same inclusion criteria: anal canal squamous cell carcinoma of ≥4 cm or pelvic node involvement treated with conformal radiotherapy (45 Gy/25 fractions plus a boost) and concomitant fluorouracyl and cisplatin at weeks 1 and 5. A multivariate analysis of potential factors (patients, tumors, and treatments) was carried out through Cox proportional hazard model. Results were presented as hazard ratio (HR)., Results: 387 patients were included. In multivariate analysis, age over 55 years (HR = 0.62, p = 0.013), the increase of circumferential tumor spread (between 1/3 and 2/3 and more than 2/3 compared to less than 1/3) (respectively 1.97, p = 0.015 and 2.94, p < 0.001), the skin ulceration (1.57, p = 0.03), the inguinal node involvement (1,98, p < 0.001) and the total radiotherapy dose above 60 Gy (between 60 and 65 Gy (HR = 0.37, p < 0.001) and >65 Gy (HR = 0.61, p = 0.028)) were associated with colostomy-free survival., Conclusion: Our study highlights new favorable prognostic factors such as circumferential tumor damage of less than two thirds, age over 55 years, dose escalation boost irradiation and possibly a total radiation dose between 60 and 65 Gy (but the BED dose depends on the overall treatment time). These results could be considered for better selection or stratification of the target population in future trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients., Methods: This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon's optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy., Discussion: Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA., Trial Registration: NCT02402842 , EudraCT: 2014-001789-81.

Purpose: To evaluate prospectively chronic gastrointestinal toxicity in patients with cervical cancer treated with conventional irradiation or with intensity-modulated irradiation (IMRT)., Patients and Methods: Between June 2005 and September 2013, 109 patients underwent external radiotherapy followed by brachytherapy for cervical cancer at the "Institut de Cancérologie de Lorraine". Each patient receiving IMRT was paired with a patient receiving conventional radiotherapy on the following criteria: concomitant chemotherapy, additional nodal dose, treatment of para-aortic lymph node area, age. The toxicity collection was prospective using the RTOG scale. The main objective was to compare the incidence of gastrointestinal toxicity chronic between the two groups. In a second time, the influence of dosimetric parameters on chronic GI toxicity was investigated. Comparisons of acute toxicity, chronic genitourinary toxicities, overall survival, disease-free survival were secondary objectives., Results: Sixty-six patients were able to be matched. Overall survival at 36 months was 71% in the conventional radiotherapy group against 73% in the IMRT group (P=0.54). There was no significant difference between the two groups in terms of digestive chronic toxicity (P=0.17), nor in terms acute gastrointestinal toxicities (P=0.6445) and genitourinary (P=0.5724). IMRT spared significantly small bowel (P=0.0006) and rectum (P=0.0046) from 30Gy dose, and bladder from 45Gy (P<0.001). The incidence of genitourinary toxicity was significantly different between the two groups (P=0.03) in favor of conventional radiotherapy., Conclusion: Our study does not seem to show significant difference in the occurrence of chronic gastrointestinal toxicities between the two groups. Clinical efficacy seems comparable. Larger studies with longer follow-up period should be conducted., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: Pulsed-dose-rate (PDR) brachytherapy is thought to mimic the radiobiological benefits of continuous low-dose-rate (cLDR) delivery but is safer for medical personnel. We set out to evaluate the outcomes of this technique in patients with head and neck squamous cell carcinoma., Methods and Materials: A total of 36 consecutive patients treated with PDR brachytherapy were randomly matched to 72 cLDR controls according to T-stage, tumor site, and management strategy. Local recurrence and late complications were compared between the two groups., Results: Baseline characteristics were similar in both groups. Oral cavity cancers predominated at 81%, and 89% had T1/T2 tumors. Seventy-five percent of patients underwent surgery before radiation treatment. Median followup was 59 and 30 months for cLDR and PDR patients, respectively. Three-year actuarial local recurrence-free survival was 97% and 94% for cLDR and PDR patients, respectively (p = 0.77). Three-year cumulative risk of Grade ≥2 complications was 45% and 32% for cLDR and PDR patients, respectively (p = 0.2). For cLDR, a dose rate exceeding 68 cGy/h resulted in more complications (RR 5.3, p < 0.05). Similarly, PDR patients receiving ≥75 cGy/pulse were at higher risk., Conclusions: PDR brachytherapy in head and neck squamous cell carcinoma yields comparable results to cLDR treatment. Dose rate was correlated with the risk of late complications, regardless of technique., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIV+) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30%-40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5%-8% at onset, and rates of metastatic progression after primary treatment between 10 and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16-18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80%-90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT)., Methods and Materials: Within a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center., Results: At 2 years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V60 were predictive factors for local control (p = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V60 <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4-11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control., Conclusions: This multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V60 for IR-CTV was identified as an important predictive factor for local control., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIV+) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30-40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5-8% at onset, and rates of metastatic progression after primary treatment between 10% and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16-18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80-90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Low dose-rate brachytherapy as a boost after concomitant chemoradiation therapy is a standard of care for locally advanced anal carcinoma, providing a rigorous selection taking into account the initial staging and tumor response to external beam radiotherapy. Local control is likely to be superior when the boost is performed with brachytherapy than with external beam radiotherapy. The several steps of the brachytherapy procedure are described. The standard treatment scheme is a concomitant chemoradiation therapy, including 45 Gy (1,8 Gy × 5) pelvic external beam radiotherapy and two courses of 5-fluorouracil and mitomycin-C, followed by a 15 Gy brachytherapy boost with a gap limited to 2 to 3 weeks. Higher irradiation dose for the most advanced cases has not yet demonstrated a therapeutic gain in terms of colostomy free survival. Exclusive brachytherapy for in-situ carcinoma or invasive carcinoma less than 10mm is not recommended due to a high risk of local recurrence. Pulsed dose rate brachytherapy is an alternative to low dose rate brachytherapy (iridium wires) providing the respect of the recommended dose rate (0.5 to 1 Gy/hour). High dose rate brachytherapy is still under evaluation., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Aims: To understand management strategies and outcomes of patients diagnosed with a head and neck tumour and a synchronous second cancer developed at another anatomic site., Materials and Methods: Retrospective analysis of all patients diagnosed with a head and neck carcinoma and a synchronous cancer and engaged in curative-intent treatments. To evaluate therapeutic strategies, each patient's treatment process was divided into sequential therapeutic modalities and corresponding targets (head and neck and/or synchronous tumour) were identified. Patient outcome was analysed with an intent-to-treat approach., Results: Forty-three patients were entered into the study (mean age=57.4 years). Synchronous tumours concerned the lung (57.8%), oesophagus (31.1%) or other sites (11.1%). Treatments were complex, including one to four consecutive modalities, with a mean duration of 4.6 months. When both tumours were advanced, treatments were frequently initiated with dual-spectrum chemotherapy (66.7%). In other situations, a locoregional treatment was often (81.1%) proposed immediately. When both tumours were in early stages, this initial locoregional treatment could be extended to target both tumours together (30.0%). For patients whose tumours differed in severity, this locoregional treatment targeted only one tumour (85%); priority was given to the most advanced one (76.5%). Nine patients had definitive treatment interruption. Associated risk factors were a low body mass index (P=0.03) and advanced-stage tumours (P=0.01). Thirty-one patients died (72.1%) with a median time to death of 7.7 months. The median follow-up for survivors was 46.2 months. Three-year overall survival was 33.9%. Low body mass index (P=0.001), advanced-stage synchronous tumours (P=0.03) and oesophageal primaries (P=0.03) altered the overall survival. Three-year locoregional and metastatic progression-free survival was 40.8 and 62.5%, respectively. Low body mass index (P=0.01) and advanced-stage synchronous tumours (P=0.01) increased the risk of disease failure., Conclusions: Head and neck tumours diagnosed with a synchronous cancer are a complex challenge. Despite a severe prognosis, patients who are not underweight, presenting with lower-stage tumours (especially the synchronous tumour) and without oesophageal involvement could most benefit from aggressive treatments., (Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma., Methods and Materials: We retrospectively reviewed the records (April 1991-May 2004) of patients with non-small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis., Results: 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40-84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed at 1 cm from the radius (24-35 Gy in 4-6 fractions). Mean follow-up was 30.4 months (range, 9-116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease (n = 45), local failure (n = 36), metastasis (n = 10), local failure and metastasis (n = 11), complications (n = 13), and other causes (n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival (p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival (p = 0.0001)., Conclusions: This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This case report presents a 57 years-old woman treated for a squamous cell carcinoma of the anal canal by radiochemotherapy and brachytherapy. The particularity of this case lays on the fact that she presented a mediastinal and pleural metastatic evolution three years later, which was also treated by radiochemotherapy, leading to a complete remission of 50 months. This observation is interesting for its curative treatment in metastatic cancer of the anal canal. It also illustrates the radiosensibility of anal canal cancers, including metastatic situations, and raises the contribution of PET-scanner to evaluate the response to treatment and detect a recurrence.

Both primary and recurrent squamous cell carcinoma of the head and neck are classic indications for brachytherapy. A high rate of local tumor control at the cost of limited morbidity can be achieved with brachytherapy through good patient selection, meticulous source implantation and careful treatment planning. However, no randomized trials have been performed, and there is scant evidence in the literature especially regarding practical clinical recommendations for brachytherapy for head and neck subsites. The Head and Neck Working Group of the European Brachytherapy Group (Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) therefore decided to formulate the present consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy. The use of brachytherapy in combination with external beam radiotherapy and/or surgery is also covered as well as the use of brachytherapy in previously irradiated patients. Given the paucity of evidence in the literature, these recommendations are mainly based on clinical experience accumulated by the members of the working group over several decades and the respective publications. The recommendations cover in a general part (1) patient selection, the pre-treatment work up and patient care, (2) treatment strategy, (3) target definition, (4) implant techniques, (5) dose and dose rate prescription, (6) treatment planning and reporting, (7) treatment monitoring (8) catheter removal, and (9) post-treatment patient care and follow-up. The recommendations are then specified for the classical brachytherapy tumor sites following an analogue more focussed structure (patient selection, implant technique, target definition, dose and dose rate prescription, results): lip, oral mucosa, mobile tongue, floor of mouth, oropharynx, nasopharynx, paranasal sinuses.

Purpose: To analyze the prognostic factors of loco regional control (LRC), specific survival (SS) and sphincter conservation (SC) of patients treated by curative and conservative irradiation for an epidermoid cancer of anal canal in our institution., Patients and Methods: From 1976 to 2005, 286 patients (pts) were treated by exclusive radiotherapy (180 pts) or chemo-radiotherapy (106 pts) followed by a brachytherapy boost (233 pts) or external beam radiotherapy boost (24 pts). Forty-three pts were stage I, 154 stage II, 31 stage IIIA and 53 stage IIIB., Results: The mean follow-up was 65 months (range: 1.3-250 months). The 5-years-overall survival and SS rates were 66.4% and 78.1% respectively. In multivariate analysis, tumor size (>or=40 mm) [RR=2.1], node involvement (RR=2.4), and poor response (<75%) to first course irradiation [RR=1.9], local relapse (RR=4.5) and distant metastases were factors of poor prognosis for SS. Five-years-LRC were 71.5% (88% for stage I, 69% for stage II, 77%, for stage IIIA and 60% for stage IIIB). Prognosis factors of LCR were tumor size (RR=2.5), response to first course of irradiation (RR=2.9). SC was 71% at 5 years. Prognosis factors of SC were tumor size (RR=1.9) and response to first course of irradiation (RR=2.4)., Conclusion: The results of this series are similar to those of the literature. As well as initial tumor extension, response to first course of irradiation was found as prognostic factor on LCR, SS, SC. Our results are similar to other series and brachytherapy seems not to be deleterious. Its impact to local control remains to be evaluated.

Background and Purpose: To evaluate the results of pulsed dose rate brachytherapy (PDR) in SCACC., Material and Methods: From 1996 to 2002, 71 patients (pts) with SCACC were treated with PDR brachytherapy. The median age was 61.2 years (35-88), with a sex ratio of 1 M/6.5 F. The TNM classification was: 14 T1, 41 T2, 15 T3 and 1 T4, 52 N0, 13 N1, 3 N2 and 3 N3. All the pts were M0. Treatment started with external beam irradiation to the posterior pelvis (mean dose: 45.5 Gy). Forty-seven patients received chemotherapy (neoadjuvant/concomitant or both). After an interval of 2-6 weeks, PDR interstitial brachytherapy was performed. The mean dose was 17.8 Gy to the 85% reference isodose of the Paris system., Results: Treatment was interrupted in only one pt. With a median follow-up of 28.5 months, 2-year actuarial overall survival was 90%. Fourteen relapses occurred (four distant, three regional, and seven local). Ten patients developed a grade III complication (Lent Soma scale) and two a grade IV complication (colostomy or abdominal perineal resection for necrosis)., Conclusion: PDR appears to be an effective treatment for SCACC. It is capable of reproducing the results usually observed with continuous LDR.

Purpose: The largest in vivo dosimetry study for interstitial brachytherapy yet examined was performed using new radiophotoluminescence glass dosimeters (RPLGDs). Based on the results, a dose prescription technique achieving high reproducibility and eliminating large hyperdose sleeves was studied., Methods and Materials: For 61 head-and-neck cancer patients who underwent high-dose-rate interstitial brachytherapy, new RPLGDs were used for an in vivo study. The Paris System was used for implant. An arbitrary isodose surface was selected for dose prescription. Locations of 83 dosimeters were categorized as on target (n = 52) or on nontarget organ (n = 31) and were also scaled according to % basal dose isodose surface (% BDIS). Compatibility (measured dose/calculated dose) was analyzed according to location. The hyperdose sleeve was assessed in terms of prescription surface expressed in % BDIS., Results: The spread of compatibilities was larger for on nontarget organ (1.06 +/- 0.32) than for on target (0.87 +/- 0.17, p = 0.01). Within on target RPLGDs, compatibility on <95% BDIS (0.95 +/- 0.10) was better than on > or =95% BDIS (0.84 +/- 0.18, p = 0.02). The number of patients with diameter of hyperdose sleeve > or =10 mm was increased with a dose prescription to <77% BDIS (p = 0.046). For nontarget organs, the maximal positive deviation was 84% of the calculated dose., Conclusions: Dose prescription is recommended to >77% and <95% BDIS for reproducibility and elimination of excessive hyperdose sleeve. For organs at risk, radioprotection should be considered even when calculated dose seems sufficiently low. Further development of planning software is necessary to prevent overestimation.

Background: Postoperative radiotherapy is necessary for squamous cell carcinoma (SCC) of the oral cavity with positive or close margins. The aim of the study is to define the indications of postoperative brachytherapy (BRT)., Methods: From 1979 to 1993, 82 patients with positive or close margins had postoperative BRT (58 T1-2, 24 T3-4, 45 mobile tongue, 37 floor of mouth). Forty-six patients had combined radiotherapy (RT) with a mean dose of 48 Gy, and BRT boost with a mean dose of 24 Gy. Thirty-six patients had BRT alone with a mean dose of 60 Gy. BRT was performed with interstitial low dose rate Iridium 192., Results: Overall survival (OS), cause-specific survival (CSS), and local control (LC) at 5 years were, respectively, for T1-2/N0N- with BRT, 75%, 85%, and 88%,and with RT-BRT 70%, 92%, and 92%; for T1-2/N+ with RT-BRT, 44%, 67%, and 78%; for T3-4/N- with RT-BRT, 42%, 90%, and 80%; and for T3-4/N+ with RT-BRT, 22%, 43%, and 57%. Prognostic factors for OS, CSS, and LC were N+ (p

Concomitant radiotherapy (5FU-MMC) was proved to be useful in locally advanced anal canal carcinoma. Nevertheless, it remains 30% of failures after this conservative treatment. The tolerance and efficiency of a neoadjuvant chemotherapy (5-FU-CDDP) were validated by a phase II trial including 80 patients, which obtained 73% of colostomy free survival and 70% of relapse free survival at 3-year follow-up. Its usefulness is studied in an ongoing phase III trial, as well as the dose escalation of the boost, from 15 Gy to 25-25 Gy. The results of the 101 first included patients are studied by an intermediate analyze. In July 2003, 222 patients were enrolled by 33 investigating centres out of the 350 planned patients until the end of the trial in December 2004.

Purpose: To collect data on the health-related quality of life (QOL) of long-term survivors and to determine to what extent QOL might be an appropriate end point in the comparison of treatment options in oropharyngeal carcinoma., Methods and Materials: All patients treated between 1992 and 1998, in two French comprehensive cancer centers, by brachytherapy (BT) +/- external beam radiotherapy (EBRT) or surgery plus RT, or exclusive EBRT for T1-T3 (International Union Against Cancer staging system) oropharynx squamous cell carcinoma, were included. QOL was measured once in disease-free patients at least 2 years after treatment initiation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module were self-administered by all participating patients. Sociodemographic data were collected using a questionnaire specifically designed for the study. The association between the QOL scores of the various treatment-, disease-, and patient-related variables was performed through bivariate analysis and then by multivariate analysis. The mean QOL scores of the EORTC QLQ-C30 questionnaire were compared with the mean scores in the general population., Results: Of the 159 eligible patients, 113 agreed to participate (97 men and 16 women, median age 61 years, range 41-83). The initial treatment was EBRT plus BT in 49 patients, surgery plus RT in 27, and EBRT alone in 37. The median follow-up time was 62 months (range 24-110). Compared with the general population, the three scores indicating the most impaired QOL were emotional and social functioning and fatigue. The clinical significance of global QOL impairment was borderline. The physical functioning, role functioning, and pain scores did not significantly differ from those of the general population. In multivariate analysis, the initial treatment had no significant influence on any dimension of QOL, except global QOL and emotional functioning. Surprisingly, surgery plus RT, as the initial treatment, favorably influenced the emotional functioning score and EBRT plus BT negatively influenced the global QOL score. None of these treatment modalities influenced any symptom scales. Patient selection was, at least partially, responsible for these paradoxical results., Conclusion: The results of this study bring original and useful data about the QOL of long-term survivors of oropharynx carcinoma. In these patients, the QOL was significantly impaired, particularly in its psychosocial dimensions. The level of symptoms and functioning (except global QOL and emotional) was similar whatever the initial treatment. These results suggest the importance of coping processes. In a trial comparing treatment options from a long-term perspective, survival remains the most relevant end point, and a QOL evaluation should be a secondary end point. More prospective studies on QOL in head-and-neck cancer patients are needed to determine new strategies for rehabilitation management.

Purpose: To analyse toxicity and response to a new scheme of neoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced anal canal squamous-cell carcinoma (ACC)., Patients and Methods: Eighty patients with an ACC > 40 mm and/or with lymph node involvement were included (1 T1, 52 T2, 14 T3, 13 T4, 18 N0, 30 N1, 32 N2-N3). Two cycles of 5-fluorouracil (5-FU) and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (+/- inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a one to two month gap (15-20 Gy). The median follow-up was 29 months., Results: One patient died of a pulmonary embolism on day 4. All patients received the entire treatment, with reduced 5-FU doses in 27% of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were observed. No toxic death occurred. Complete response (CR) and partial response (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28% after RT-CT and 93% and 5% after treatment completion (including 4 abdomino-perineal resections). The three-year actuarial overall, tumour-specific, colostomy-free, relapse-free, disease-free and event-free survivals were 86%, 88%, 73%, 70%, 67% and 63%, respectively., Conclusions: Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achieved CR. The long-term results confirm the durability of local control and low toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradiation, on local control and colostomy-free survival.

Purpose: To prospectively evaluate the feasibility of pulsed dose rate (PDR) brachytherapy to mimic the continuous low dose rate (cLDR) iridium wire technique in head and neck carcinomas., Materials and Methods: A series of 30 patients were included from June 1995 to May 1998. The primaries were located in the oral cavity (four T1, seven T2 and two T3), the velotonsillar arch (eight T1 and eight T2) and the posterior wall (one T3). Thirteen were irradiated by exclusive brachytherapy (dose, > or =45 Gy). The PDR delivered 0.5 Gy/pulse, one pulse/h, day and night, to mimic cLDR irradiation., Results: The implantation was feasible for all the patients, usually easy and of good quality. The mean duration/pulse was 13 min, with a mean source activity of 171 mCi. Patient tolerance was poor in nine cases. Sixteen patients could receive the whole PDR treatment with a total ranging from 30 to 120 pulses without any problem. Seven had short breakdowns (< or =6 h). Seven had definitive breakdowns, but could end the irradiation by manual afterloading of iridium 192 wires. The radioprotection was better (or complete), except for one patient. Most of the breakdowns were related to kinking or flattering of the tube., Conclusions: PDR is feasible in head and neck carcinomas, but necessitates improvement of the quality and control of the plastic tubes.

Epidermoid anal canal carcinomas are radio- and chemosensitive tumors. Within a few decades, conservative treatment has replaced mutilating surgery as standard therapeutic practice. Exclusive high-dose radiotherapy remains the standard treatment of early stages T1-T2 N0 smaller than 4 cm. Three phase III trials demonstrated the benefits of combined chemotherapy and irradiation on the local efficacy and colostomy-free survival. Mitomycin C and 5 FU were delivered on weeks 1 and 5 of the irradiation. Concomitant 5 FU and CDDP regimen and neoadjuvant chemotherapy were evaluated on phase II trials. Ongoing intensification phase III trials are described.

Purpose: To evaluate the efficacy of postoperative brachytherapy alone (brachy) for Stage T1-2 squamous cell carcinomas (SCC) of the floor of mouth (FM) and the oral tongue (OT) with close or positive margins., Methods and Materials: Between 1979 and 1993, 36 patients with T1-2 N0 (24 T1, 12 T2) OT (19), and FOM (17) SCC with close or positive margins following surgery underwent postoperative brachy. Mean patient age was 56 years (range 37-81) and sex ratio was 3.5:1 male:female. Mean surgery to brachy interval was 36 days (range 16-68). The technique used was interstitial Iridium-192 ((192)Ir) brachytherapy with plastic tubes and manual afterloading. Mean total dose was 60 Gy (range 50-67.4) at a mean dose rate of 0.64 Gy/h (range 0.32-0.94). Mean patient follow-up was 80 months., Results: The 5-year actuarial overall and cause-specific survivals of the entire group were 75% and 85%, respectively. The local control was 88.5% at 2 years, with a plateau apparent after 23 months. Of the 4 local relapses, 2 were salvaged with surgery and external beam radiotherapy (EBR). No tumor or treatment factors, including tumor size, margin status, disease site, or radiation dose, were correlated with local control. The 2 head and neck second primaries underwent curative treatment on nonirradiated tissue. One patient developed a grade 3 sequelae (bone and soft tissue necrosis). Grade 2-3 chronic sequelae were seen in 7 of 17 and 3 of 19 FOM and OT tumors, respectively (p = 0.09)., Conclusion: Postoperative brachy is a promising approach in T1-2 N0 OT and FOM SCC with close or positive margins. This approach is associated with high rate of locoregional control and low risk of chronic sequelae, obviates major surgery, avoids potential sequelae of EBR (xerostomia, dysgueusia, fibrosis), and avoids treatment of second head and neck primary on nonirradiated tissues.

Background and Purpose: To evaluate the feasibility of pulsed dose rate (PDR) brochytherapy in squamous cell anal canal carcinoma (SCACC)., Materials and Methods: In this study a series of 19 patients with SCACC were included between 1995 and 1997. All patients were treated with curative intent with external beam radiotherapy (EBRT) (44-50 Gy) and one or two cycles of concomitant fluorouracilcisplatinum. After a gap of 2-3 weeks PDR interstitial brachytherapy was performed with a rigid needles technique. The dose was between 10-25 Gy (PARIS system)., Results: All patients are alive. No severe grade 3-4 toxicity was encountered. One local relapse one metastatis were seen in two distinct patients. There was no dysfunction of the after loading machine., Conclusion: The feasibility of PDR brachytherapy appears good in SCACC. It is an attractive alternative to low dose rate brachytherapy.

Purpose: We wanted to study the influence of the time factor in a combination of external irradiation and brachytherapy from a retrospective study of 370 squamous cell carcinomas of soft palate and tonsil., Patients and Methods: From 1977 to 1993, 370 soft palate and tonsillar carcinomas were treated at the Centre Alexis Vautrin. All patients received external irradiation (ERT) with a minimum dose to the tumour of 45 Gy, followed by low dose rate brachytherapy by Iridium 192 using the technique of plastic tubes; 22 patients received neo-adjuvant chemotherapy. We treated 85 T1, 159 T2, 117 T3 and nine T4 or TX carcinomas; 128 of these had palpable nodes. There were 267 men and 24 women. The median age was 55 years (range 33-81 years)., Results: The median duration of the total treatment was 57 days. The rate of local control was 88% at 5 years when the treatment time was 7 weeks and 74% when it was 9 weeks (P = 0.001). The rates of overall survival at 5 years were 63 and 44%, respectively (P < 0.0001). For the interval between external irradiation and brachytherapy the series was divided into three groups, i.e. patients treated with a delay inferior or equal to 16 days (2 weeks), patients for which the interval was between 16 and 20 days and patients treated with a delay greater than 20 days (3 weeks). The rates of local control and overall survival at 5 years were not significantly different in the two first groups so we amalgamated these two groups and compared them with the third group. In this way the time cut-off for the delay between external irradiation and brachytherapy was 20 days. At 5 years, the rate of local control was 85% for the group for which the interval was inferior to 3 weeks and 73% when the delay was greater (P = 0.01). The rates of overall survival at 5 years were 59 and 38%, respectively (P < 0.001). Multivariate analysis confirmed that protraction of treatment was a factor for poorer local control. This factor was independent of the other prognostic factors., Conclusion: The total duration of irradiation and the delay between external irradiation and brachytherapy were significant prognostic factors for local control and overall survival of soft palate and tonsil carcinomas. The overall duration should not be greater than 7 weeks (external irradiation, 5 weeks plus a delay of 12-15 days between ERT and brachytherapy). The delay should never be greater than 20 days, but a boost should be considered to make up for the loss of local control.

Purpose: The detection of an infraclinical primary by tonsillectomy in case of cervical lymph node of an epidermoid carcinoma with unknown primary after a radical neck dissection, allows avoiding irradiation of the normal larynx. The aim of this study is to quantify the rate of tonsil primary to justify this procedure., Methods and Materials: From 1969 to 1992, 87 patients had a tonsillectomy as part of the workup for cervical nodal metastasis of an epidermoid carcinoma with unknown primary. The mean age was 57 years (range: 39-75 years) and the sex ratio was 8.6. Sixty-seven patients had a single cervical adenopathy (17 N1, 30 N2a, 5 N3, 15 Nx), and 20 patients multiple cervical adenopathies (17 N2b, 3 N2c). The treatments included always an irradiation to the node areas (50 Gy), and to the pharyngolarynx in case of normal tonsil (50 Gy), or to the tonsil if it was the primary (50 Gy with a brachytherapy boost of 20-25 Gy). In this last case, the larynx could be protected., Results: Tonsillectomy never induced specific complication. Out of 87 patients, 26% had a tonsil primary. There was not specific histological differentiation in this group. In the 67 patients with a single cervical adenopathy, 31% had a tonsil primary (6 N1, 7 N2, 1 N3, 7 Nx). It was a subdigastric adenopathy in 38%, a submandibular in 28% and a midjugulocarotidian in 23%. Among the 17 patients N2b, none had a tonsil primary. In the three patients N2c, two presented a tonsil carcinoma (two subdigastric nodes)., Conclusion: Tonsillectomy allows avoiding irradiation of normal larynx in 26% of patients who have a cervical lymph node with unknown primary. It should be performed in case of a single node of the subdigastric, midjugulocarotidian or submandibular area or bilateral subdigastric adenopathies.

Purpose: Few series have described treatment results of anal margin tumors as defined in the UICC 87 classification. The purpose of this article is to describe experience with an uncommon condition in a single cancer center., Methods and Materials: From 1971 to 1995, 32 patients with carcinoma of the anal margin were irradiated with a curative intent, and 31 were followed-up for more than 6 months (mean = 4.5 years). There were 9 T1, 15 T2, 7 T3, and 1 T4 (vulvar), with 26 N0 and 6 N1. There was a minor invasion of the lower canal in 17 patients. The histological types were 24 squamous cell and 7 basocellular carcinomas, and 1 Paget's disease. The treatment was a combined External Beam Irradiation (EBI) and Brachytherapy (BT) in 16 patients, an exclusive BT in 12 patients, and an exclusive EBI in 4 patients. No prophylactic inguinal irradiation was delivered., Results: The 5-year actuarial results are as follows: overall survival = 67%, specific survival = 89%. The only prognostic factor was nodal involvement (p < 0.001). T-stage, T-size, age, sex, and treatment schedule were not significant. The overall local control was 77%, and 93.5% after salvage. Two N0 patients relapsed in inguinal areas (one was salvaged). Twenty-six percent presented a Grade 3 or 4 late complication, necessitating a temporary colostomy in only one patient. The sphincter conservation reached 84% for the whole series, 80% for patients followed-up 5 years or more, and 89% for cured patients., Conclusion: Results are similar to other series, and seem better than for anal canal cancer. We recommend exclusive irradiation. There is no data recommending concomitant chemotherapy. Depending on the tumor size and localization, the tumor boost can be applied by EBI or BT. Surgery is reserved for small tumors far from the canal or for salvage. An inguinal prophylactic bilateral irradiation should be recommended for N0, with tumors over 4 cm.

The aim of this study was to analyse the role of post-operative brachytherapy (BT) in a group of patients with a high risk of local relapse (positive or narrow surgical margins) for squamous cell carcinoma of the mouth floor (SCCFM). A comparison with post-operative external beam irradiation (EBI) in a group of patients with standard risk of local relapse for SCCFM with free margins is performed to estimate the benefit of BT. From 1979 to 1992, an initial group of 32 patients with SCCFM (12, T1-2; 20, T3-4x) received an Ir 192 low dose rate BT using plastic tubes (+EBI for 20 patients) after surgery with positive or close margins. BT was applied in one or two planes to the surgical scar. The mean dose of BT was 57 Gy (range: 50-60) for exclusive BT and 22 Gy (range: 15-30) when a boost was applied (mean EBI dose = 50 Gy). During the same period, 36 patients had post-operative external irradiation alone after satisfactory surgical resection. Excluding the post-operative margin, these two groups were comparable for other prognostic factors. The mean follow-up was 46 months (range: 5-145) with a minimum follow-up of 2 years. For BT and EBI groups, the 5-year results (Kaplan-Meier) were, respectively, overall survival 62% and 43%, local control 81% and 60% (P = 0.09) (log-rank) and severe complications 4/32 and 1/36. Post-operative BT achieves good local control for patients with narrow or positive margins by increasing the dose to the surgical scar, with good tolerance. Given these encouraging results, we confirm this treatment for these patients.

Background and Purpose: Although supracervical hysterectomy is becoming a rare procedure, there are still many women with retained cervical stump. The purpose of this retrospective study was to assess the results of treatment in patients with carcinoma of the cervical stump., Materials and Methods: From 1974 to 1990, 77 patients were treated for an infiltrating carcinoma of the cervical stump. This group accounted for 6.6% of the cervical carcinoma diagnosed during the same period. The pathological examination showed, 91% of squamous cell carcinomas and 9% of adenocarcinomas. FIGO stage distribution was: I (35%), II (45%), III (18%), IV (2%). According to the stages, the treatment used a combination of external beam radiation therapy (EBRT) with plesiobrachytherapy (PBT), and in a few cases, patients underwent surgery or interstitial brachytherapy (IBT). In patients with bulky tumour or advanced stage and/or lymphatic node involvement, EBRT was first delivered. Most of Stage I and Stage II patients, began their treatment with PBT. All stages included, 95% of the patients were treated by exclusive radiation therapy. Complications were classified according to the recommendations of late effects normal tissues (LENT) scoring system described by the EORTC/RTOG., Results: Three-year pelvic control was achieved in 59 of 77 patients (76.6%) in the whole series. Three-year pelvic control probabilities were 77% (95% CI: 66-85%), and 89% (95% CI: 72-96%), 73.7% (95% CI: 65-88%) and 56% (95% CI: 28-80%) in the whole series and in Stage I-III tumour patients, respectively. The 5-year and 10-year overall survival probabilities in the whole series, were 66.4% (95% CI: 55-76%) and 61.2% (95% CI: 50-72%), respectively. Ten patients (12.8%) developed 17 late complications distributed as follows: G1, nine patients (11.7%); G2, five patients (6.5%); G3, one patient (1.3%); and G4, two patients (2.6%)., Conclusions: Treatment results are similar both in patients with carcinoma of the cervical stump and in patients with carcinoma of the intact uterus. Indeed, it is sometimes difficult to perform a correct PBT application because of the pelvic anatomic modifications induced by the subtotal hysterectomy and its consequences on the new organisation of critical organs into the treated volume.

Unlabelled: We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermoid cancer of the anal canal (ECAC) the prognostic factors of locoregional control (LRC), survival, late severe complications (LSC), and sphincter conservation (SC)., Methods and Materials: From 1976 until 1994, 118 patients presenting with an ECAC were conservatively treated (mean age, 65 years). According to the 1987 International Union Against Cancer (TNM) classification, they were: 19 T1, 70 T2, 22 T3, 7 T4, 94 N0, and 24 N1-3. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5-fluorouracil and mitomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 192Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdominoperineal resection (APR). The mean follow-up was 6 years., Results: At 5 years the overall survival was 60%, and specific survival (SS) was 75%; it was 94% for T1, 79% for T2, 53% for T3, and 19% for T4. In multivariate analysis, tumor size (> or = 4 cm), node involvement, and no response to the EBI were factors of poor prognosis for SS. Thirty-two locoregional recurrences occurred of which 21 were local recurrences in the 106 patients treated by a conservative schedule. Only tumor size and response to the EBI were prognostic factors on multivariate analysis for local and LRC. A total of 17 patients presented with LSC (Grade 3, 16 patients; and Grade 4, 1 patient), which was treated by APR in 4 patients and colostomy in 11 (of which 7 were definitive). The only significant prognostic factor for LSC in the multivariate analysis was the total extrapolated response dose of irradiation. The definitive rate of SC after conservative treatment in cured patients was 100% for T1, 82% for T2, 58% for T3, and 100% for T4. Since 1989, improvements of the technique have allowed reduction of the LSC in maintaining the same local control., Conclusion: The results of this series are similar to those of the literature. The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case to obtain better tumor control, with as few sequelae as possible, to yield a better rate of SC.

Brachytherapy has confirmed its prevailing role in conservative treatment of oral cavity carcinomas. To describe late toxicity in long-term surviving patients, comparisons with other series are necessary. Study of series of patients implanted for floor of the mouth or mobile tongue shows the need for more detailed data. Dental prophylaxy and lead protection of the mandibule, good indications and techniques of brachytherapy are necessary to avoid late complications. Some treatment factors have proved to be of good prognosis for late complications through multivariate analysis of large series treated with lr 192 wires, using the Paris system, eg, dose rate lower than 0.5 or 0.7 Gy/h, intersource spacing smaller than 1.2 or 1.5 cm, treated surface less than 12 cm2, lineic activity less than 1.5 mCi/cm, less than 1 cm diameter hyperdose, and use of mandibular lead protections. Tumor volume and location to the floor of mouth lead to higher risk of complications. Knowledge of treatment-related factors is important, with the development of new afterloading projectors allowing to control the dose rate and correct small inhomogeneities. High-dose rate exclusive brachytherapy is not recommended. More precise and reproducible classification should be used to report complications in series leading to publications in the future, thus allowing to compare results, reduce complication rates and improve the quality of life.

Our study focuses on a series of 1344 cases of carcinoma of the oral cavity and oropharynx treated between 1973 and 1992. Brachytherapy was always performed with iridium 192, either alone or in combination with external-beam irradiation or with surgery for the treatment of the primary tumor. For the oral cavity, we studied 565 cases of mobile tongue. The local control and overall survival rates, respectively, at 5 years are as follows: for T1, 92% and 70%; for T2, 62% and 42%; and for T3, 50% and 29%. For the subgroup T1T2NO, there was a better prognosis for treatment by brachytherapy of the primary lesion alone (p < 0.0001). Two hundred seven cases of floor-of-mouth carcinoma have been reported. The T3T4 patients were not considered surgical candidates. The local control and overall survival rates, respectively, at 5 years are as follows: for T1, 97% and 71%; for T2 72% and 42%; and for T3, 51% and 35%. Ninety-seven patients were treated by postoperative brachytherapy. These were patients for whom the margins after surgery were positive or narrow. A technique termed the modified bridge is described for lesions located in the mandible. Carcinomas of the buccal mucosa are rare in our country; only 42 cases were treated in this comparison of two techniques, and the overall survival rate was 48%. Epidermoid carcinomas of the oropharynx have nearly always been treated by a combination of external-beam irradiation and brachytherapy because of the bilateral node risk. Seventy-two patients with epidermoid cancers of the base of the tongue had an overall survival rate of 44%. The tonsil, soft palate, and pillars benefited from the use of the loop technique of brachytherapy combined with external-beam irradiation. Three hundred sixty-one patients were treated. Among these patients were two groups with different prognoses. Patients with tonsil, soft palate, and posterior pillar carcinomas had a local control rate of 84% and an overall survival rate of 57%. Conversely, the anterior pillar and the pharyngoglossal sulcus have a local control rate of only 65% and an overall survival rate of 38%. Statistical analysis revealed the prognostic factors for local control. The complications were classified into four grades: minor (20%), moderate (9%), major (4%), or inducing death (0.2%). The bone complications of grade 2 or 3 are more frequent for the floor of the mouth than for other locations.

From 1977 to 1991, we treated 361 carcinomas of the velotonsillar region, either by brachytherapy alone (18 cases), or by an association of external radiotherapy and brachytherapy (343 patients). The latter was performed using a special technique with iridium wires in plastic tubes with afterloading. The primary was the tonsil in 128 patients, the soft palate in 134 patients. We numbered also 9 posterior pillars, 63 anterior pillars and 27 velotonsillar sulcus. According to the UICC staging system (28), we classified the patients in 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3 and 9 Nx. The results at 5 and 10 years show respectively: local control (LC) 80% and 75%, locoregional control 75% and 70%, global survival 53% and 28%, specific survival 63% and 52%. The univariate study shows at 5 years a better local control for T1-T2 (87%) than for T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (66%) with p = 0.002, this is the same for global survival (59% versus 42%, p = 0.002). The two groups were individualised according to the primary. Inside each of these groups, the prognosis is identical for different localisations, which allows to put them together. We can therefore distinguish a group A which includes the tonsil, the soft palate and posterior pillar. This group has a better prognosis (controls and survivals) than group B (anterior pillar and velotonsillar sulcus) (p < 0.002). The tumours extended to the mobile tongue, the base of the tongue or the velotonsillar sulcus have a poorer prognosis than those without propagation or with an upwards propagation (p < 0.002). The statistical study of radiobiological factors that can influence the tissular repair shows that there are less recurrences if the duration of treatment is inferior to 55 days and if the interval between external irradiation and brachytherapy is inferior to 20 days. A sufficient safety margin seems also necessary for a good local control. The dose rate within the limits used does not seem to influence the local control and the total dose delivered to the tumour, but this is not surprising since the highest doses are given to the tumours with the smallest regression during external irradiation. The multivariate study for local control shows that the most significant factors are the T, the tumoral localisation and the total duration of treatment. For complications (classified in 4 stages), the dose rate is the most significant factor.

Out of 332 epidermoid carcinomas of the base of the tongue treated in Centre Alexis Vautrin from 1978 to 1992, 136 received. a treatment with a curative intent. The median age was 58 years, the median follow-up was 57 months. We numbered 55 T1-T2 and 81 N0 or N1. From the therapeutic point of view, the patients were classified into three groups: in group 1 (45 cases), they were treated by external irradiation only (median dose: 71 Gy); in group 2 (72 cases), they were treated by external irradiation and brachytherapy (the mean dose delivered by external irradiation was 50 Gy, and by brachytherapy, the mean dose was 30 Gy with a mean dose rate of 55 cGy/h); in group 3 (19 cases), they were treated by a radiosurgical association, the surgical resection was always mutilating and completed by an external irradiation (55 Gy), 8 patients received an associated barrier brachytherapy. Thirty-nine patients presented a local failure, 50 a locoregional evolution. The rate of local control at 5 years was 19% for group 1, 39% for group 2 and 32% for group 3. The calculation of the equivalent biologic dose in group 1 allows to separate this population into two subgroups whose survival rates are significantly different (at 3 years: 26% and 6%, P = 0.02) and shows the influence of fractionation and treatment time. The actuarial survival at 3 years is 19% for group 1, 55% for group 2 and 45% for group 3, the survival without evolution is 33% for group 1, 66% for group 2 and 72% for group 3. For the whole series, we numbered 18 complications of grade equal or superior to 2 (healing in more than 3 months, or sequelae or death) out of which four bone complication and 14 tissular complications that occurred in a mean delay of 9 months. Because of technical modifications, there have been no grade complications for implantations performed from 1989. The prognosis remains poor for cancers of the base of the tongue. The rates of survival are still low when they are treated by external irradiation only. There seems to exist a slight advantage in favour of the radio-brachytherapy association compared to the radiosurgical association with a lower rate of sequelae and mutilations.

Purpose: To report our experience using brachytherapy in buccal mucosa carcinoma with particular attention on the technique of implantation used and on the elective treatment to the lymph nodes., Methods and Materials: From 1973 to 1991, 42 patients (36 T1 T2 T3, 35 NO) were treated for epidermoid carcinoma of the buccal mucosa as the first site of head and neck cancer. To study the local control, the group of 36 T1-3 patients was divided into two groups according to the brachytherapy technique used: the parallel wires technique and the loop technique (M. Pernot). The latter consists of making a loop of Iridium wire encircling the tumor, the curved part acting as a barrier for the posterior part of the cheek (site of recurrence). The group of 35 NO patients was individualized to evaluate the necessity of an elective node treatment. Twenty-three patients had no elective treatment to node areas, 8 an external radiotherapy, and 4 a neck dissection., Results: Overall survival of these 42 patients was 63% at 2 years and 47.5% at 5 years. Specific survival was 77.5% at 2 years and 73.6% at 5 years. Survival without recurrence was 58% at 2 years and 54% at 5 years. Eighty-three percent of the recurrences occurred during the first year. There were six local recurrences on the 14 T1-3 patients treated with the parallel wires technique and 1 on the 22 T1-3 patients treated with the loop technique (6 out of 7 in the posterior part of the buccal mucosa). The local control at 5 years was 91% with the loop technique vs. 58% with the parallel wires technique (p = 0.01). Among the 23 NO patients with no elective treatment, 6 had a nodal failure (5 T2 and 1 T1 of 2 cm). Out of the 8 NO patients treated by radiotherapy, 3 had a nodal failure. The four NO patients treated by surgery were controlled., Conclusion: Brachytherapy using the loop technique is the local treatment of choice for tumors < or = 5 cm. Elective treatment of the neck lymph nodes is required in patients with a lesion > 1 cm and neck dissection may be preferable to external radiotherapy.

The study bears on 672 infiltrating carcinomas of the cervix treated from 1977 until the end of 1991, by a radiosurgical combination (311 patients) or by exclusive irradiation (361 patients). The radiosurgical series includes mostly stages IB and II and patients under 50 years because of the therapeutic protocol. Most of the patients aged over 50 years and all stages III were treated by exclusive irradiation. External beam irradiation was most often performed in 4 fields by linear accelerator of 12 and 25 MeV. Uterovaginal brachytherapy used the technique of molds. In 55 cases, a complementary interstitial brachytherapy was applied on residual node. A computer dosimetry was made for each patient with calculation of the doses delivered to organs at risk and to node areas (points of calculation ICRU n degrees 38). The results at 5 years are as follows for the total series: locoregional control (LRC) 79%, specific survival (SS) 73%, overall survival 70%. For stage I, the LRC of the radiosurgical series is 92%, that of the series of exclusive irradiation 87% (no significant difference, neither for SS if we consider the tumoral size); For stage II, the LRC is 70% in the radiosurgical series and 79% in the series of exclusive irradiation. There is no difference if proximal stage II is compared. Conversely, for distal stage II, the difference is very significant in favour of exclusive irradiation (LRC 31%/77%, SS 26%/70%, p < 0.006). If we consider the results according to age, the difference for distal stage II comes mostly from patients under 50 years and especially those aged 40 years or under. For stage III, the LRC is 61% for patients over 50 years and 34% for those aged 50 years or under (p = 0.006). As the nodes, the results of surgical pieces and lymphadenectomy are studied. The patients under 40 years in stages II and III present more metastases than others (p = 0.003). Among the therapeutic factors, the dose rate and the treatment duration were particularly studied. A detailed study of the complications is made for the radiosurgical series as for the series of exclusive irradiation according to the French Italian glossary of complications as well as a study of the factors inducing them.

Purpose: Our aim was to study the results and the complications of this series of 207 patients treated from 1976 to 1992 and to compare them with the results of the literature., Material and Methods: The treatment consisted of a combination of external beam irradiation (EBI) (to the tumor and the node areas) and complementary brachytherapy to the primary tumor in 105 cases. In 102 cases, brachytherapy only was delivered to the tumor with or without neck dissection of the node areas. The brachytherapy was performed mostly with the hairpin technique in the beginning (in 61 cases) and subsequently the plastic tube technique with iridium wires. The dosimetry followed the Paris system rules. There were 41% T1, 48% T2, 8% T3, 2% T4 and 1% Tx with 83% N0, 12% N1, 3% N2, 2% N3. Ninety-one percent of patients were male and 9% were female., Results: The local control at 5 years is 97, 72 and 51%, respectively, for T1, T2, T3. The specific survival (without the patients dead of intercurrent disease or second cancer) was 88, 47 and 36%, and the overall survival at 5 years was 71, 42 and 35%. Of note, approximately one third of patients died of intercurrent disease or second cancers (70 patients = 34%). Significant factors that can influence the results are: for local control, the size of the lesion T1/T2/T3 (p < 0.0001); for the locoregional control, the absence of node involvement. The following factors are not significant: age and sex (age significant for survival). The significant treatment factors are the safety margin (p < 0.0003), brachytherapy only on T for T2N0 (p = 0.01). A total duration of treatment of less than 50 days is also significant. The spacing and the total dose (higher dose for large tumors) were not found to be significant. The complications were classified into four grades: grade 1, 17% (median healing, 2 months for soft tissue complications and 5 months for bone complications); grade 2, 12%; grade 3, 6% (frequently requiring surgical resection); grade 4, 0.5% (death, one case). In this series, for the complications, the dose rate, the spacing and the total dose were found not to be significant., Conclusion: Carcinomas of the floor of mouth treated by exclusive irradiation have a rather good prognosis and the number of grade 2 and 3 complications remains acceptable. Exclusive brachytherapy is preferable to the combination of EBI plus brachytherapy for T1T2N0.

Purpose/objective: We tried to reduce the number of local recurrences after surgery and external beam irradiation (EBI) in carcinoma of the oral cavity, when margins were positive or close., Material and Methods: From 1980 to 1992, we treated 97 cases of carcinomas of the oral cavity by postoperative brachytherapy. Surgery was combined with EBI+brachytherapy in 51 cases and with brachytherapy alone in 46 cases. We treated 29 T1, 34 T2, 30 T3T4 and four Tx (73% were N0 at first examination and 23% had positive nodes). The type of surgery is analysed. Brachytherapy was performed in one or two planes along the surgical scar. If the mandibular rim was resected, especially when the tongue or the remaining floor were sutured to the internal face of the inferior lip or to the buccal mucosa, the bridge technique was used. To decrease the dose to the inferior part of the mandible, the bridge was modified thanks to experimental dosimetry., Results: At 5 years, the local control (LC) is 89%, the locoregional control (LRC) 82%, the specific survival (SS) 74% and the overall survival (OS) 67%., Complications: We noted 19% of grade 1 (minor), 12% of grade 2 (moderate) and 6% of grade 3 (major) complications., Conclusion: Compared with the results of the literature, we think that postoperative brachytherapy can improve classical radiosurgical results in selected cases with a risk of local recurrence.

Unlabelled: The study includes 346 carcinomas of the oral cavity (244 mobile tongues and 102 floors of mouth) treated by brachytherapy alone at primary tumor. We noted 199 T1, 131 T2, 14 T3 and 2 TxNx. Among T1, 36 patients had a neck dissection as well as 73 T2. Brachytherapy was performed according to the Paris system. In 59 cases, the curage on the lesion side was a radical neck dissection, in 14 cases a functional neck dissection and in 45 cases a submaxillary and submental dissection. A combined controlateral neck dissection was performed in 20 cases. A complementary irradiation of the node areas was given in 28 cases., Results: for T1, the local control (LC) is 96%, the locoregional control (LRC) 83%, the specific survival (SS) 88%, and the overall survival (OS) 73%. For T2, LC 85%, LRC 70%, SS 75%, OS 52%. For T3, LC 64%, LRC 44%, SS 25%, OS 18%. The difference is very significant between T1 T2 T3 (p < 0.006) for results concerning N0, it is not significant between the N1 in each category, but their number is too low to reach a degree of significancy. In the 36 neck dissection specimens of T1, we found only in 7 cases positive nodes and in the 73 specimens of T2, 24 cases of positive nodes. A detailed study is reported. Tumoral, node or both recurrences are summarized (see table IV). Node recurrences are more frequent in patients without neck dissection than in those with neck dissection for T1, T2, N0, but this is significant only for LRC, SS and OS between patients with negative nodes on neck dissection and those with positive nodes (p < 0.0001). No significant difference was found between OS and SS for patients T1, T2, N0 with positive systematic neck dissection and those with a neck dissection differed until the node recurrence. Among T1, T2, T3, we noted more metastases in patients who presented a recurrence than in others. In conclusion, for patients treated by brachytherapy alone to the primary lesion, it seems desirable to perform a systematic neck dissection if there are adenopathies on initial examination. The dissection can be delayed for small tumors T1 N0 and low T2 N0 if the patients are followed-up regularly. However, a systematic dissection must be advised for high T2 N0 and T3 N0 given the frequency of the node involvement and the risk of metastases.