Pierre Scalliet

Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)

BACKGROUND Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. METHODS After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. FINDINGS The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726). INTERPRETATION Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.

Postoperative Radiotherapy After Radical Prostatectomy: A Randomised Controlled Trial (EORTC Trial 22911)

Summary Background Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We dida randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation withprostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. Methods After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-seepolicy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks).Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positivesurgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-freesurvival. Analysis was by intention to treat. Findings The median age was 65 years (IQR 61–69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74·0%, 98% CI 68·7–79·3

RELEVANCE OF A SYSTEMATIC GERIATRIC SCREENING AND ASSESSMENT IN OLDER PATIENTS WITH CANCER RESULTS OF A PROSPECTIVE MULTICENTRIC STUDY

BACKGROUND To evaluate the large-scale feasibility and usefulness of geriatric screening and assessment in clinical oncology practice by assessing the impact on the detection of unknown geriatric problems, geriatric interventions and treatment decisions. PATIENTS AND METHODS Eligible patients who had a malignant tumour were ≥70 years old and treatment decision had to be made. Patients were screened using G8; if abnormal (score ≤14/17) followed by Comprehensive Geriatric Assessment (CGA). The assessment results were communicated to the treating physician using a predefined questionnaire to assess the topics mentioned above. RESULTS One thousand nine hundred and sixty-seven patients were included in 10 hospitals. Of these patients, 70.7% had an abnormal G8 score warranting a CGA. Physicians were aware of the assessment results at the time of treatment decision in two-thirds of the patients (n = 1115; 61.3%). The assessment detected unknown geriatric problems in 51.2% of patients. When the physician was aware of the assessment results at the time of decision making, geriatric interventions were planned in 286 patients (25.7%) and the treatment decision was influenced in 282 patients (25.3%). CONCLUSION Geriatric screening and assessment in older patients with cancer is feasible at large scale and has a significant impact on the detection of unknown geriatric problems, leading to geriatric interventions and adapted treatment.

Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma

PURPOSE The analysis of complications in a prospective randomized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented. METHODS AND MATERIALS Between 1985 and 1988, 204 patients with Stage I and limited Stage II cervical cancer were randomized to receive one of two preoperative brachytherapy low-dose rates (0.4 and 0.8 Gy/hr). The objective of this trial was to determine the benefits, if any, of the higher-dose rate within the therapeutic arsenal for this patient population, in terms of survival, local control, and complications. The type and severity of all complications were evaluated according to a common glossary and a strict follow-up schedule was established given that the treatment of cervical cancer is multidisciplinary, involving gynecologists, surgeons, and radiotherapists. RESULTS Overall survival: 85% at 2 years and local control: 93% at 2 years, were similarly distributed between the two groups. Regardless of their nature and severity, 139 and 175 complications were observed among 63% and 75% of patients, in the 0.4 and 0.8 Gy/h dose rate groups respectively. Gynecologic and urinary complications were the most frequent (38% and 28% of all complications), followed by vascular (15%), digestive (10%), nervous (5%) and cutaneous (5%). A total of 14 and 17 severe complications (Grade 3) were observed in 7% and 13% of patients, respectively in the 0.4 and 0.8 Gy/h dose rate groups (p = 0.12). Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups: 62% and 72% at 2 years (p = 0.27). When the first complication and its evolution were considered (early complications), the prevalence of complications was not significantly different between the two groups: 28% vs. 34% at 2 years (p = 0.31). In this prospective trial, patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up. When successive complications and their evolution were taken into account, the prevalence of complications was significantly greater in the higher-dose rate group: 30% vs. 45% at 2 years (p = 0.03). CONCLUSION The results of this trial showed that long-term effects of treatment, when represented by prevalence of complications over time, were more frequent in the higher dose rate group. This underlines the importance of the regular follow-up of patients and of coding, not only the occurrence of all complications, but also their evolution over time.

Molecular Response to Cetuximab and Efficacy of Preoperative Cetuximab-Based Chemoradiation in Rectal Cancer

PURPOSE To characterize the molecular pathways activated or inhibited by cetuximab when combined with chemoradiotherapy (CRT) in rectal cancer and to identify molecular profiles and biomarkers that might improve patient selection for such treatments. PATIENTS AND METHODS Forty-one patients with rectal cancer (T3-4 and/or N+) received preoperative radiotherapy (1.8 Gy, 5 days/wk, 45 Gy) in combination with capecitabine and cetuximab (400 mg/m2 as initial dose 1 week before CRT followed by 250 mg/m2 /wk for 5 weeks). Biopsies and plasma samples were taken before treatment, after cetuximab but before CRT, and at the time of surgery. Proteomics and microarrays were used to monitor the molecular response to cetuximab and to identify profiles and biomarkers to predict treatment efficacy. RESULTS Cetuximab on its own downregulated genes involved in proliferation and invasion and upregulated inflammatory gene expression, with 16 genes being significantly influenced in microarray analysis. The decrease in proliferation was confirmed by immunohistochemistry for Ki67 (P = .01) and was accompanied by an increase in transforming growth factor-alpha in plasma samples (P < .001). Disease-free survival (DFS) was better in patients if epidermal growth factor receptor expression was upregulated in the tumor after the initial cetuximab dose (P = .02) and when fibro-inflammatory changes were present in the surgical specimen (P = .03). Microarray and proteomic profiles were predictive of DFS. CONCLUSION Our study showed that a single dose of cetuximab has a significant impact on the expression of genes involved in tumor proliferation and inflammation. We identified potential biomarkers that might predict response to cetuximab-based CRT.

Does sucralfate reduce the acute side effects in head and neck cancer treated with radiotherapy? A double blind randomized trial

BACKGROUND AND PURPOSE We evaluated sucralfate, well-known in the treatment of gastric ulcers, in relation to its possible reduction of radiation-induced acute complications in the treatment of head and neck cancers. MATERIALS AND METHODS One hundred two patients were randomized in a double-blind placebo-controlled prospective setting. All patients were treated to a minimum dose of 55 Gy in 5 weeks. Oral intake of sucralfate was started at the beginning of radiotherapy and continued during the whole treatment at a dose of 1 g six times a day. All patients were scored according to a scoring system developed in our department. Weight was checked once a week. RESULTS Comparing the time course of the mean scores for subjective intolerance, mucositis, dysphagia, dermatitis and nausea, no statistically significant differences between the two treatment arms (sucralfate, n = 38; placebo, n = 45) were observed. The mean weight loss in the sucralfate arm was 1.6 +/- 3.4 kg while it was 1.3 +/- 2.0 kg in the placebo arm. Apart from gastrointestinal upset, the administration of sucralfate did not cause any side-effects. CONCLUSION This trial produced no clinical evidence indicating that the oral intake of sucralfate reduces the acute radiation-induced side-effects. Therefore, we do not recommend the prophylactic use of sucralfate in patients with head and neck cancer treated by radiotherapy.

Phase III trial comparing two low dose rates in brachytherapy of cervix carcinoma: Report at two years

This Phase III randomized trial examined the effect of two low dose rates (0.73 or 0.38 Gy.h-1) on the local control, survival, relapse-free survival, complications, and secondary effects in the treatment of cervical cancers. A total of 204 Stage Ib or II cervical carcinoma patients were included between January 1985 and September 1988. Treatment consisted of uterovaginal 137Cs irradiation followed by surgery. The two groups were similar for age, tumor stage and medical or surgical history. Their brachytherapy parameters were also similar (60 Gy pear dimensions, dose to critical organs, total kerma, etc....) There were no differences in the short-term effects or therapeutic outcome. However, overall complications and side effects observed after 6 months were significantly more frequent (p < 0.01) in the higher dose rate group.

Which RBE for iodine 125 in clinical applications

The problem of the selection of a RBE value for 125I is discussed for clinical applications in interstitial therapy. Microdosimetric studies indicate that the emission of the 125I has a y spectra similar to X-rays of 12-140 keV (conventional X-rays), but differs from 60Co, 137Cs gamma-rays and high energy X-rays. The radiobiological data available show RBE values ranging from 1 to 2.4 for 125I (reference beam 60Co). Although obtained with different biological systems and endpoints, RBE values of 1.15-1.20 are in general observed for high doses and high dose rates. On the other hand, higher RBE values (up to 2) are observed at low doses or low dose rates, which is consistent with theoretical and microdosimetric data.

A multi-institutional analysis comparing adjuvant and salvage radiation therapy for high-risk prostate cancer patients with undetectable PSA after prostatectomy.

BACKGROUND AND PURPOSE In men with adverse pathology at the time of radical prostatectomy (RP), the most appropriate timing to administer radiotherapy (RT) remains a subject for debate. To determine whether salvage radiotherapy (SRT) upon early prostate-specific antigen (PSA) relapse is equivalent to immediate adjuvant radiotherapy (ART) post RP. MATERIAL AND METHODS 130 patients receiving ART and 89 receiving SRT were identified. All had an undetectable PSA after RP. Homogeneous subgroups were built based on the status (±) of lymphatic invasion (LVI) and surgical margins (SM), to allow a comparison of ART and SRT. Biochemical disease-free survival (bDFS) was calculated from the date of surgery and from the end of RT. The multivariate analysis was performed using the Cox Proportional hazard model. RESULTS In the SM-/LVI- and SM+/LVI- groups, SRT was a significant predictor of a decreased bDFS from the date of surgery, while in the SM+/LVI+ group, there was a trend towards significance. From the end of RT, SRT was also a significant predictor of a decreased bDFS in three patient groups: SM-/LVI-, SM+/LVI- and SM+/LVI+. Gleason score >7 showed to be another factor on multivariate analysis associated with decreased bDFS in the SM-/LVI- group, from the date of surgery and end of RT. Preoperative PSA was a significant predictor in the SM-/LVI- group from the date of RP only. CONCLUSIONS Immediate ART post RP for patients with high risk features in the prostatectomy specimen significantly reduces bDFS after RP compared with early SRT upon PSA relapse.

Anatomical bases for the radiological delineation of lymph node areas. Part III : pelvis and lower limbs

Cancer spreads locally through direct infiltration into soft tissues, or at a distance by invading vascular structures, then migrating through the lymphatic or blood flow. Although cancer cells carried in the blood can end in virtually any corner of the body, lymphatic migration is usually stepwise, through successive nodal stops, which can temporarily delay further progression. In radiotherapy, irradiation of lymphatic paths relevant to the localization of the primary has been common practice for decades. Similarly, excision of cancer is often completed by lymphatic dissection. Both in radiotherapy and in surgery, advanced knowledge of the lymphatic pathways relevant to any tumor location is an important information for treatment preparation and execution. The third part of these series describes the lymphatics of the pelvis and the lower limb. It Provides anatomical bases for the radiological delineation of lymph nodes areas in the pelvic cavity and in the groin. It also offers the first original classification for labeling the intrapelvic nodes, grouped in seven paired volumes (called levels I-VII), functionally linked with one another and lower abdominal levels by eight potential drainage pathways.