T.D. Nguyen

Management of primary anal canal adenocarcinoma: A large retrospective study from the Rare Cancer Network

PURPOSE Primary adenocarcinoma of the anus is a rare tumor. The current standard treatment consists of abdominoperineal resection (APR). The aim of this Rare Cancer Network study was to evaluate the prognostic factors and outcome after the three most commonly used treatment approaches. METHODS AND MATERIALS This multicenter study collected data from 82 patients: 15 with T1 (18%), 34 with T2 (42%), 22 with T3 (27%), and 11 with T4 (13%) tumors according to the TNM classification (International Union Against Cancer, 1997). Patients were separated into, and analyzed according to, three treatment categories: radiotherapy/surgery (RT/S group, n = 45), combined radiochemotherapy (RT/CHT group, n = 31), and APR alone (APR group, n = 6). The main patient characteristics were evenly distributed among the three groups. RESULTS The actuarial locoregional relapse rate at 5 years was 37%, 36%, and 20%, respectively, in the RT/S, RT/CHT, and APR groups (RT/S vs. RT/CHT, p = 0.93; RT/CH vs. APR, p = 0.78). The 3-, 5-, and 10-year overall survival rate was 47%, 29%, and 23% in the RT/S group, 75%, 58%, and 39% in the RT/CHT group, and 42%, 21%, and 21% in the APR group (RT/CHT vs. RT/S, p = 0.027), respectively. The 5- and 10-year disease-free survival rate was 25% and 18% in the RT/S group, 54% and 20% in the RT/CHT group, and 22% and 22% in the APR group (RT/CHT vs. RT/S, p = 0.038), respectively. Multivariate analysis revealed four independent prognostic factors for survival: T stage, N stage, histologic grade, and treatment modality. CONCLUSION Primary adenocarcinoma of the anal canal requires rigorous management. Multivariate analysis showed that T and N stage, histologic grade, and treatment modality are independent prognostic factors for survival. We observed better survival rates after combined RT/CHT. We also recommend using APR only for salvage treatment.

Management of Adenoid Cystic Carcinoma of the Breast: A Rare Cancer Network Study

BACKGROUND Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC. METHODS Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy). RESULTS With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT. CONCLUSION Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery.

Evaluation économique prospective de la radiothérapie guidée par l'image des cancers de la prostate dans le cadre du programme national de Soutien aux Thérapeutiques Innovantes et Coûteuses

PURPOSE The main objective of the economical study was to prospectively and randomly assess the additional costs of daily versus weekly patient positioning quality control in image-guided radiotherapy (IGRT), taking into account the modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A secondary objective was to prospectively assess the additional costs of 3D versus 2D imaging with portal imaging for patient positioning controls. PATIENTS AND METHODS Economics data are issued from a multicenter randomized medico-economics trial comparing the two frequencies of patient positioning control during prostate IGRT. A prospective cohort with patient positioning control with PI (control group) was constituted for the cost comparison between 3D (IGRT) versus 2D imaging. The economical evaluation was focused to the radiotherapy direct costs, adopting the hospitals point of view and using a microcosting method applied to the parameters that may lead to cost differences between evaluated strategies. RESULTS The economical analysis included a total of 241 patients enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128 with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to weekly controls, the average additional cost per patient of daily controls was €847 (CBCT) and €179 (markers). Compared to PI, the average additional cost per patient was €1392 (CBCT) and €997 (fiducial markers) for daily controls; €545 (CBCT) and €818 (markers) in case of weekly controls. CONCLUSION A daily frequency for image control in IGRT and 3D images patient positioning control (IGRT) for prostate cancer lead to significant additional cost compared to weekly control and 2D imaging (PI). Long-term clinical assessment will permit to assess the medico-economical ratio of these innovative radiotherapy modalities.

Hyperfractionated radiotherapy with or without misonidazole: results of a prospective randomized study in stage III-IV squamous cell carcinoma of the head and neck

From 1979 to 1980, 52 patients with Stage III-IV squamous cell carcinoma of the head and neck were included in a prospective randomized study on hyperfractionated radiotherapy with or without misonidazole. The radiotherapeutic schedule consisted of two weeks of treatment split by a rest-period of one month, 6 X 1.1 Gy fractions per day for 5 consecutive days (total dose: 2 X 33 Gy/30 f/5 d). Total dose of misonidazole was 12 g/m2 administered daily in 1.2 g/m2 fractions. The overall tolerance of misonidazole was good, with a neuropathy rate of 5.7%. Local control, recurrence and 3 year survival rates did not statistically differ between the two groups. The randomized trials published at the present time, including our own, suggest that misonidazole has no beneficial effect with classical, concentrated or multiple fractions per day radiotherapy.

Relation between responses to induction chemotherapy and subsequent radiotherapy in advanced or multicentric squamous cell carcinomas of the head and neck

Between 1984 and 1986, 85 consecutive patients with Stage III-IV or multi-centric squamous cell carcinoma of the head and neck were given three courses of chemotherapy followed by curative external radiotherapy. Induction chemotherapy consisted of either DDP (100 mg/m2, d 1) + 5 FU (1 g/m2/d, d 1-5, continuous infusion) or DDP (100 mg/m2, d4) + Etoposide (60 mg/m2/d, d 1-5, intravenously). Radiotherapy was delivered 70 Gy over 7 weeks in gross tumor and palpable nodes and 50 Gy over 5 weeks in clinically negative nodal areas. Complete response (CR) rates of both the chemotherapies were 39% for the primary and 20% for the nodes whereas partial response (PR) rates were 22% and 40%, respectively. Six months after completion of radiotherapy, 70% of the primaries and 63% of the nodes achieved complete response. The analysis of responses to chemotherapy on one hand and to subsequent radiotherapy on the other shows that the response to chemotherapy can be regarded as predictive for subsequent radiotherapy (p less than 0.001) except in T1-T2 tumors. In these early stages radiotherapy can be efficacious despite a previous failure of chemotherapy (p less than 0.01).

The use of a concomitant electron boost (field in the fieldtechnique) in large cervical node metastases over a shortened period

Seven patients with large cervical node metastases were treated at the Institut Jean-Godinot using a particular scheme of accelerated irradiation. Conventional Cobalt-60 radiotherapy was prophylactically delivered to extended volumes of the neck (50 Gy in 25 fractions over 5 weeks). Within the fields of cobalt irradiation, an electron beam field was added to increase the daily dose from 2 to 3 Gy (Fletchers field in the field technique). The increment of dose was limited to nodal area. Since no interval separated the two irradiations, involved areas were considered to receive 70 Gy in 25 fractions over 5 weeks and non-clinically involved areas to receive 50 Gy in 25 fractions over 5 weeks. In all the cases, the malignant mass diameter exceeded 5 cm. Acute tolerance was good and no major late injury was observed during the 18 months minimum follow-up period. At the end of the treatment, a complete disappearance of the tumor was observed in six out of seven cases. At the present time, four patients are still alive without evidence of disease. Slight acceleration of irradiation by the use of a concomitant electron boost is easily feasible and may provide an improvement in local control and therapeutic ratio of large cervical malignant masses in the neck.

Exclusive radiotherapy for non-small cell lung cancer. A retrospective multicentric study

Summary Purpose To evaluate the daily practice of management of early inoperable lung cancer (stage I). Materials and methods The analysis was based on a questionnaire which was sent to participated centers. Between 1982 and 1994, 123 patients with an early stage I inoperable lung cancer were treated with definitive irradiation in the different institutions. The survival distributions were estimated by the Kaplan-Meier method. The following covarties were analyzed: age, gender, Karnofsky status, symptoms, diagnostic work-up, T stage, tumour size, tumour location, histology, respiratory and cardiac contra-indication. The univariate analysis was performed using log-rank test. Cox regression models were used to find the independent prognostic factors. Results : The 2 and 5-year survival rates were 34% and 8% respectively. The 5-year local failure rate was 42% for T1 and 82% for T2. In a multivariate analysis, the most important prognostic factors for survival were the performance status and the stage. After adjustment for these two covariates, the total dose delivered had no impact for the range of doses used in this series. Conclusions Our poor data outlined the needs for better radiation technique and for a better staging system.

Neoadjuvant chemotherapy and irradiation in multiple synchronous squamous cell carcinoma of the upper aero digestive tract

Twenty-four patients with multiple, synchronous carcinoma of the head and neck, lung or esophagus, were treated with induction chemotherapy followed by irradiation to involved areas. Chemotherapy regimen consisted of cisplatinum either alone, or in combination with 5-FU or etoposide. Subsequently, external radiotherapy, 60-65 Gy and 70-75 Gy to the mediastinum and the head and neck areas, respectively, was carried out. Following chemotherapy, three patients (12.5%) had a complete clinical remission in both cervical and mediastinal sites. That rate was significantly increased by radiotherapy (66%). Tolerance was fair or mild even though half of the patients needed a rest break during irradiation. Follow-up ranges from 24 to 38 months. The median survival is 12 months and the actuarial survival rates are 45% and 5% at 12 and 24 months, respectively. It is suggested that induction chemotherapy will not drastically improve the overall prognosis of multiple squamous cell carcinoma of the upper aero digestive tract and that external irradiation remains a major part of treatment which should not be reduced in treated volumes, or in total dose delivered.

Impact of adjuvant hormonotherapy on radiation-induced breast fibrosis according to the individual radiosensitivity: results of a multicenter prospective French trial

Background To evaluate risk of severe breast fibrosis occurrence in patients treated by breast-conserving surgery, adjuvant radiotherapy and hormonotherapy (HT) according to individual radiosensitivity (RILA assay). Results HT– and RILAhigh were the two independent factors associated with improved breast-fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with RILAlow and HT+ than in patients with RILAhigh and HT– (75.8% and 100%, respectively; p = 0.004, hazard ratio 5.84 [95% confidence interval (CI) 1.8–19.1]). Conversely, BFFS at 36 months was comparable in patients with RILAhigh and HT+ and in patients with RILAlow and HT– (89.8% and 93.5%, respectively; p = 0.39, hazard ratio 1.7 [95% CI 0.51–5.65]), showing that these two parameters influenced independently the occurrence of severe breast fibrosis. BFFS rate was not affected by the HT type (tamoxifen or aromatase inhibitor) and timing (concomitant or sequential with radiotherapy). Conclusions HT and RILA score independently influenced BFFS rate at 36 months. Patients with RILAhigh and HT– presented an excellent BFFS at 36 months (100%). Materials and methods Breast Fibrosis-Free Survival (BFFS) rate was assessed relative to RILA categories and to adjuvant HT use (HT+ and HT–, respectively) in a prospective multicentre study (NCT00893035) which enrolled 502 breast cancer patients (456 evaluable patients). Breast fibrosis was recorded according to CTCAE v3.0 grading scale; RILA score was defined according to two categories (<12%: RILAlow; ≥12%: RILAhigh).