[Hodgkin lymphoma and target definition guidelines]. / Radiothérapie « involved node ¼ et « involved site ¼ des lymphomes hodgkiniens : quels volumes cible ?

Treatment for stage I and II Hodgkin lymphoma is based on a combination of chemotherapy and radiotherapy, with a high successful cure rate. Now, the aim is to decrease toxicity rates. Positron-emission tomography scan is recommended as pretreatment baseline and is very useful to define precisely target volumes for planning radiation therapy. Based on these changes were developed guidelines for modern radiation therapy called involved node and « involved site ¼.

Local recurrence after ductal carcinoma in situ breast conserving treatment. Analysis of 195 cases.

PURPOSE: Ductal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival. PATIENTS AND METHODS: This study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS+RT), presenting local recurrences, with a 156-month median follow-up. RESULTS: Eighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P=0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P<0.0007). CONCLUSION: Invasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed.

Ductal carcinoma in situ of the breast in younger women: a subgroup of patients at high risk.

BACKGROUND: After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS. METHODS: From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy. RESULTS: 37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype (p = 0.004), histological size more than 10 mm (p = 0.011), necrosis (p = 0.022) and positive margin status (p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%. CONCLUSION: High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free.

Contribution of surgery in patients with bulky residual disease after chemoradiation for advanced cervical carcinoma.

AIM: To report the outcome of 30 patients who underwent surgery after concomitant chemoradiation for locally advanced cervical cancer with residual disease > or = 2 cm. METHODS: From 1988 to 2004, 143 patients with FIGO stage IB2-IVA cervical cancer underwent surgery after concurrent chemoradiotherapy. Among them, 30 had a residual cervical tumour > or = 2 cm prior to surgery. Surgery consisted in a simple or radical hysterectomy (n=15) or in a pelvic exenteration (n=15). Endpoints were recurrence and distant metastasis rates, overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Analysis included FIGO stage, response to chemoradiation, para-aortic lymphatic status or type of surgery: palliative (remaining disease after surgery) or curative (no evidence of remaining disease after surgery). RESULTS: Surgery has been only palliative in 11 cases. Pelvic recurrences occurred in 8 patients after a median interval of 8.8 months. Distant metastases occurred in 8 patients after a median interval of 13 months. So far, 16 patients have died (53.3%). The 3-year and 5-year OS rates are 64.9% and 55.6%, respectively, for the 19 patients who had a curative surgery. The DFS rate is 50.8% at 3 and 5 years in this latter group. Overall 12 patients (40%) are alive and free of disease after a median follow-up of 32.5 months. CONCLUSIONS: Adjuvant surgery may improve the outcome of patients with bulky residual tumour after chemoradiation for locally advanced cervical cancer, allowing a 5-year OS of 55.6% after curative intervention.

[Ductal carcinoma in situ of the breast. Analysis of 882 cases]. / Carcinome canalaire in situ du sein. Analyse de 882 cas.

OBJECTIVE: This study assesses the results of "current clinical practice" among 882 women treated in nine French Cancer Centers from 1985 to 1995 for pure ductal carcinoma in situ (DCIS) of the breast. METHOD: Median age was 53 years (range 21-87); 177 (20%) patients underwent mastectomy (M), 190 (22%) conservative surgery alone (CS) and 515 (58%) conservative surgery with radiotherapy (CS + RT). RESULTS: The crude 7-year local relapse (LR) rates were 2%, 31% and 13% among the M, CS and CS+RT subgroups (p<0.0001). All four LR after M were invasive as well as 31 (52%) out of 59 and 40 (61%) out of 66 in the CS and CS+RT groups. Distant metastases occurred in 1%, 3% and 1% of the three treatment groups. No LR factors were found in the M group. Among women treated with CS, the 7-year LR rates were 36%, 31% and 30% among women aged 40 or less, 41 to 60 and 61 or more (NS). For women treated by CS+RT, the LR rates in these age subgroups were 33%, 13% and 8%, respectively (p<0.0001). Patients with negative, positive or uncertain margins had 7-year LR rates of 26%, 56% and 29% respectively if treated with CS (p=0.02) and 11%, 23% and 9% if treated with CS+RT (p=0.0008). RT reduced LR rates by 65% in all histological subgroups, but more particularly in comedocarcinoma and mixed cribriform/papillary subgroups. The 7-year rate of contralateral breast cancer was 7%, identical in all subgroups. CONCLUSION: Mastectomy remains the safest treatment for women with DCIS, with a 98% 7-year control rate. After conservative surgery, RT reduces very significantly LR rates, according to the NSABP B-17 and EORTC 10853 randomized trial results. The RT benefit is present in all clinical/histological subgroups, but its magnitude varies. Young age (<40 years) and incomplete excision are the most important LR risk factors.

[Multicenter study on dose escalation with conformal and conventional radiotherapy for the treatment of localized prostatic cancer. Preliminary results of tolerance and quality of life]. / Etude multicentrique d'escalade de dose par radiothérapie conformationnelle pour le traitement du cancer localisé de la prostate. Résultats préliminaires de la tolérance et de la qualité de vie.

OBJECTIVE: To study the safety of conformal radiotherapy dose escalation up to 80 Gy for curative treatment of prostate cancer. MATERIAL AND METHODS: A multicentre trial sponsored by the PHRC include 164 patients under the age of 75 years with stage T1b-T3 N0 M0 prostatic adenocarcinoma, between 1995 and 1998. The prostate was treated at 5 dose levels: 18 patients at 66 Gy, 28 at 70 Gy, 49 at 74 Gy, 48 at 78 Gy, 21 at 80 Gy. The acute and delayed toxicity was graded according to a multidisciplinary glossary. Quality of life was evaluated before and one year after treatment using the EORTC QLQ-C30 questionnaire and additional questions. RESULTS: 89% and 55% of mild or moderate gastrointestinal and urinary adverse effects were observed during treatment, respectively. At long-term follow-up, of the 162 evaluable patients, 12.3% presented grade 2 adverse effects and 2.5% presented grade 3 adverse effects (1 case of haematuria, 2 urethral strictures, 1 bladder neck lesion) with no significant difference between the various dose levels. Two successive quality of life questionnaires were available for 119 patients: tiredness, pain and dyspnoea increased in parallel, but non-significantly in the groups receiving conventional doses or high doses. The proportion of patients reporting sexual activity without endocrine therapy decreased from 48% before treatment to 35% one year later. The proportion of patients with no clinical or laboratory signs of progression was higher in the high-dose group. CONCLUSION: No significant difference was observed between conventional dose levels and high dose levels in terms of toxicity or quality of life. As the adverse effects were acceptable, a randomized trial comparing 70 Gy and 80 Gy has been initiated.

Combined brachytherapy and surgery for early carcinoma of the uterine cervix: analysis of extent of surgery on outcome.

PURPOSE: The aim of this retrospective study was to evaluate the survival data and rates and patterns of complications and recurrences for patients who had early uterine cervix carcinoma and underwent brachytherapy and subsequent surgery. METHODS AND MATERIALS: Between January 1990 and December 1997, 192 women with cervical carcinoma (Stages IA2 with vascular invasion [n = 28], IB1 [n = 144], and IIA [n = 20]) underwent brachytherapy, delivering 60 Gy and then hysterectomy with external iliac lymphadenectomy. Piver class I, II, and III hysterectomies were performed on 136, 38, and 18 patients, respectively. Adjuvant chemoradiotherapy was delivered to patients with positive lymph nodes. RESULTS: The median follow-up time was 61 months. After brachytherapy, a pathologically complete response (CR) was observed in 137 (71.3%) of 192 women. The distribution of CRs according to tumor stage was as follows: Stage IA2, 24 (85.7%) of 28; Stage IB1, 105 (72.9%) of 144; and Stage IIA, 8 (40%) of 20. Patients with Stage IB1 cancer had 13 lymph node metastases (9%), as did 6 with Stage IIA disease (30%). Pelvic recurrences occurred in 9 (4.6%) of the 192 patients; in 3, local relapses were associated with relapses at distant sites. Ten patients had systemic relapses (5.2%). Recurrences at distant sites were more frequent (p < 0.02) in partial responders, and other recurrences were more frequent in patients with lymph node metastases (p < 0.04). The overall 5-year disease-free survival rate was 91.2% (96.2% for Stage IA2, 91% for Stage IB1, and 84.4% for Stage IIA cancers). The class of hysterectomy did not influence the outcome. Late complications occurred in 28 patients (Grade 1, 24 [12.5%]; Grade 2, 4 [2%]; and Grade 3, 1 [0.5%] of 192 patients). CONCLUSIONS: Combined treatments resulted in high local control and low morbidity rates in patients with early-stage cervical carcinoma. Limited surgery seemed to be adequate after intracavitary therapy.

Dose escalation with 3D-CRT in prostate cancer: French study of dose escalation with conformal 3D radiotherapy in prostate cancer-preliminary results.

PURPOSE: To evaluate the feasibility of dose escalation in a multi-institutional study in prostate cancer patients. METHODS AND MATERIALS: Between October 1995 and October 1998, 164 patients with localized adenocarcinoma of the prostate were treated with 3-dimensional conformal radiotherapy at one of five French institutions. The dose of radiation was escalated from 66 to 80 Gy (ICRU point). The maximum dose to the rectal wall was limited to 75 Gy. RESULTS: Results were compared in two groups, one (group 1) receiving the standard dose (n = 46 patients; 66 to 70 Gy) and the other (group 2) receiving the escalated dose (n = 118 patients; 74 to 80 Gy). There was no difference in the characteristics of patients between the two groups. The mean follow-up time was 32 months in group 1 and 17.5 months in group 2. No statistical difference between the two groups was observed in the incidence of late gastrointestinal and urinary toxicities. The probability of achieving a posttreatment prostate-specific antigen nadir of

[Radiochemotherapy of uterine cervix cancers. Recent data]. / Radiochimiothérapie des cancers du col utérin. Données récentes.

Low-stage uterine cervix carcinoma can be treated by either surgery, radiation therapy or combined treatments with high cure rates ranging from 90 to 95% for stage IB1 tumors. However, the standard treatment, combining external beam plus intracavitary radiation, fails to control the progression of the disease in 35 to 90% of patients with locally advanced cervical cancer. No substantial improvements have been made in the treatment of these tumors in the past two decades. The addition of concurrent 5-FU in a phase III study failed to improve the results in the overall patient population, but the five-year DFS was significantly better in a subset of patients (tumor > 5 cm and IB/IIA or medial parametrial IIB disease). Concurrent chemoradiation and adjuvant chemotherapy with epirubicin showed, in a phase III study, a significantly longer DFS in patients treated with chemotherapy despite the same long-term local tumor control. After many phase II studies, five phase III studies have recently demonstrated a 40 to 60% reduction in the relative risk of recurrence with cisplatin-containing chemoradiation. Across these studies, the risk of death was reduced by 30 to 50%. The benefit was less clear in patients with stages III-IV tumors than in patients with lower stages associated with poor prognostic factors. Haematologic and gastrointestinal toxicity of chemoradiation was greater than that of radiotherapy alone. However, late side effects were similar in the different treatment groups. These results must be confirmed with a longer follow-up. The importance of concurrent chemotherapy during the brachytherapy procedure should be analyzed. It has yet to be determined which chemotherapy regimen achieves the most favorable therapeutic ratio.

Safety and efficacy of splenic irradiation in the treatment of patients with idiopathic myelofibrosis: a report on 15 patients.

Splenic irradiation in idiopathic myelofibrosis (IMF) has often been use d in selected situations when other therapies were unefficient or contraindicated. This could improve quality of life of patients, but literature remains rare in this field. We have assessed the impact of splenic irradiation in 15 patients with IMF. All of them were no longer responsive to usual treatments, and they presented at least one of the following features: constitutional symptoms, splenic pain, large splenic size, and anemia requiring >2 units of red blood cell transfusion per month. The planned schedule of radiotherapy consisted in daily fractions of 0.4-1 Gy. The median dose of radiotherapy per treatment was 9.8 Gy (range, 0.6-30.5). The overall response rate was 59% with a median duration of 10 months (range, 1-19). Splenic irradiation was more effective on constitutional symptoms, splenic pain, and spleen size. The best responses were noted when full doses of radiotherapy could be delivered, and when patients were previously fewly transfused. Splenic irradiation effectively palliates IMF-related symptoms, and constitute an alternative therapy for patients refractory to usual treatments.

Brachytherapy and vaginal hysterectomy for low-stage uterine cervix carcinoma.

OBJECTIVE: The aim of this study was to assess safety and efficiency of a limited vaginal hysterectomy after brachytherapy in patients with early uterine cervix carcinoma without unfavorable prognostic factors. All tumors were less than 1.5 cm in diameter. MATERIAL AND METHODS: Between October 1992 and December 1995, 22 patients with low-stage uterine cervix carcinoma (stage Ia2 with vascular invasion, 3 cases; stage Ib1, 19 cases) were included in this study. Patients underwent the following procedures: single utero-vaginal brachytherapy after a previous negative laparoscopic lymphadenectomy (median number of lymph nodes: 12) followed 6 weeks later by a limited vaginal hysterectomy. RESULTS: Two mild intraoperative complications were noted. Venous hemorrhage (100 cc) occurred in one patient during lymphadenectomy and another patient experienced bladder injury during hysterectomy. These two complications were successfuly controlled with no need for laparotomy. Only one late complication was observed and was evaluated as a bladder grade G2(b) according to the Franco-Italian glossary. With a 30 (22-50) month follow-up, no recurrence was reported. CONCLUSION: These results appear promising in patients with very early cervix carcinoma but remain to be confirmed on a larger scale.

Thallium-201 perfusion scintigraphy in the evaluation of late myocardial damage in left-side breast cancer treated with adjuvant radiotherapy.

PURPOSE: To evaluate late myocardial damage after adjuvant radiotherapy using a mixed-beam (photons plus electrons) technique to treat the internal mammary lymph nodes in left-side breast cancer. METHODS AND MATERIALS: A bicycle ergometer stress test coupled with thallium-201 perfusion scintigraphy and analysis by single-photon computed tomography (CT) was performed on 19 patients treated with left-side breast/chest wall and internal mammary radiation for breast cancer between 1987 and 1993. To be sure that we would evaluate late toxicity caused by the irradiation, patients had to fulfill the following eligibility criteria: left-side breast cancer, treatment between 1987 and 1993 and no recurrence during follow-up, age < or = 75 years, no known risk for coronary artery disease, no previous chemotherapy, internal mammary field treated with an association of photons and electrons, and CT scan-based treatment planning. RESULTS: Median age at scintigraphy was 59 years. Two patients did not reach optimal exercise level and were not evaluable. Among the 17 evaluable patients representing 91.6 patient years of follow-up, there were no perfusion defects by visual or quantitative analysis. CONCLUSION: The mixed-beam technique seemed to spare the heart from harmful irradiation and to protect the myocardium. Results need to be confirmed on the long-term use of this technique.

[Splenic irradiation in myeloid hemopathies: evaluation and toxicity]. / Irradiation splénique dans les hémopathies myéloides: évaluation et toxicité.

PURPOSE: Splenomegaly occurs frequently in patients with myelofibrosis (MF) or chronic myelogenous leukemia (CML), indicating significant splenic metaplasia. Symptomatic radiation therapy can be delivered, but the best irradiation scheme is still unknown. Results of splenic irradiation in patients with myelofibrosis or chronic leukemia were retrospectively analyzed. PATIENTS AND METHODS: There were 24 patients: 15 presented with MF and 9 with CML. Median irradiation doses were 9.8 and 7.7 Gy, respectively. The hematologic toxicity was moderate (except for platelets in the acute phase of the disease). RESULTS: No toxicity was observed. Various factors predictive of the response to radiation therapy are described. While high (around 14 Gy) radiation therapy dose appears necessary for MF and should be started before the increase in transfusion need, huge splenomegalies should be excluded in regard to CML. As for other cases, the optimal dose is still unclear, but should probably be high enough, ie, around 10 Gy. CONCLUSION: To further study and better understand biological mechanisms underlying response to radiotherapy in patients with MF, prospective radio-chemotherapy phase II trials should be conducted in both CML and MF patients.