M.A. Crommelin

Risk, severity and predictors of physical and psychological morbidity after axillary lymph node dissection for breast cancer

The aim of this study was to investigate the nature and severity of the arm complaints among breast cancer patients after axillary lymph node dissection (ALND) and to study the effects of this treatment-related morbidity on daily life and well-being. 400 women, who underwent ALND as part of breast cancer surgery, filled out a treatment-specific quality of life questionnaire. The mean time since ALND was 4.7 years (range 0.3-28 years). More than 20% of patients reported pain, numbness, or loss of strength and 9% reported severe oedema. None of the complaints appeared to diminish over time. Irradiation of the axilla and supraclavicular irradiation were associated with a 3.57-fold higher risk of oedema (odds ratio (OR) 3.57; 95% confidence interval (CI) 1.66-7.69) causing many patients to give up leisure activities or sport. Women who underwent irradiation of the breast or chest wall more often reported to have a sensitive scar than women who did not receive radiotherapy. Women <45 years of age had an approximately 6 times higher risk of numbness of the arm (OR 6.49; 95% CI 2.58-16.38) compared with those > or = 65 years of age; they also encountered more problems doing their household chores. The results of the present study support the introduction of less invasive techniques for the staging of the axilla, sentinel node biopsy being the most promising.

INTRAOPERATIVE ELECTRON BEAM RADIATION THERAPY FOR LOCALLY RECURRENT RECTAL CARCINOMA

PURPOSE Treatment results for locally recurrent rectal cancers are poor. This is a result of the fact that surgery is hampered due to the severance of the anatomical planes during the primary procedure and that radiotherapy is limited by normal tissue tolerance, especially after previous irradiation. This paper describes the results of a combined treatment modality in this patient group. METHODS AND MATERIALS From 1994 to 1998, 37 patients with locally recurrent rectal cancer, but without distant metastatic disease, received a combined treatment consisting of 50.4 Gy preoperative irradiation or, in case of previous radiotherapy, 30 Gy reirradiation or no irradiation, followed by radical surgery and intraoperative electron beam radiotherapy boost. RESULTS Fifteen patients received a radical resection (R0), eight a microscopic irradical resection (R1), and 14 a macroscopic irradical resection (R2). The overall 3-year local control (LC), disease-free survival (DFS), and overall survival rates were 60%, 32%, and 58% respectively. Radicality of resection (R0/R1 vs. R2) turned out to be the significant factor for improved survival (p < 0.05), DFS (p = 0.0008), and LC (p = 0.01). Preoperative (re-)irradiation is the other significant factor in survival (p = 0.005) and DFS (p = 0.001) and was almost significant for LC (p = 0.08). After external beam radiation therapy (EBRT) a significantly higher resection rate was obtained (R0/R1 vs. R2 p = 0.001). Symptomatic peripheral local recurrences have a significantly worse prognosis and higher rate of R2-resection (p = 0.0005). CONCLUSION Centralization of locally recurrent rectal cancer patients enabled the development of an aggressive multimodality treatment, which in turn led to promising results. Distant failure is still a drawback.

Feasibility and first results of multimodality treatment, combining ebrt, extensive surgery, and ioert in locally advanced primary rectal cancer

PURPOSE To assess the outcome of aggressive multimodality treatment with preoperative external beam radiation therapy (EBRT), extended circumferential margin excision (ECME) and intraoperative electron beam radiation therapy (IOERT) in patients with locally advanced primary rectal cancer. METHODS AND MATERIALS Thirty-eight patients with primary locally advanced rectal cancer, but without distant metastases, received multimodality treatment. CT-scan showed extension to other structures in 15 patients (39%) and definite infiltration into the surrounding structures in 23 patients (61%). All patients received preoperative EBRT (dose range 25-61 Gy) and 82% received 50.4 Gy. The resection types were: 12 low anterior resections (31%), 14 abdomino-perineal resections (37%), 6 abdomino-transsacral resections (16%), and 6 pelvic exenterations (16%). The IOERT dose ranged from 10 to 17.5 Gy depending on the completeness of the resection. RESULTS There was no perioperative mortality. The resection margins were microscopically negative in 31 patients (82%), microscopically positive in 4 (10%), and positive with gross residual disease in 3 patients (8%). Pelvic recurrences were observed in 5 patients (13%) including 3 IOERT infield failures. The overall 3-year local control, disease-free survival (DFS), and survival rates were 82%, 65%, and 72%, respectively. Negative resection margins were the most significant prognostic factor with regard to DFS (p = 0.0003) and distant control (p = 0.002) compared with cancer involved surgical margins. CONCLUSION A high percentage of curative resections can be achieved in this group of patients with locally advanced rectal cancers. Adding IOERT to preoperative EBRT and ECME achieves high local control rates and possibly improves survival.

Radiotherapy for locoregional relapses of rectal carcinoma after initial radical surgery: definite but limited influence on relapse-free survival and survival

A group of 95 patients, treated with irradiation for relapse after radical surgery as only initial treatment modality for a rectal carcinoma was studied. The term locoregional relapse relates to evidence of tumor recurrent in the pelvis or the perineal area. Seventy-six patients presented with locoregional relapse only, and 19 patients presented with locoregional relapse and concomitant distant metastases. All patients were irradiated at the site of locoregional relapse. Total dose of irradiation was resp. 44 Gy median (range 6-66 Gy) and 40 Gy median (range 6-50 Gy). In the group of patients with locoregional relapse only, recurrence-free survival and survival after radiotherapy were, respectively, 23% and 61% at 1 year, and 6% and 13% at 3 years. In the group of patients with concomitant distant metastases, survival after radiotherapy was even worse, 33% at one year, and nihil at 3 years. Recurrences after radiotherapy occurred early during follow-up with 75% of the recurrences being recorded during the first year of follow-up. Recurrent or persistent disease inside the irradiation volume was the most important clinical problem in both groups, being documented in, respectively, 43/76 and 7/19 (7/13 if six patients were excluded with a survival of less than 3 months from onset of therapy). In the group of patients with locoregional relapse only, using recurrence-free survival as the endpoint, dose of irradiation (p = 0.01) was a significant multivariate prognostic factor and using survival as the endpoint, dose of irradiation (p = 0.005) and grade of tumor differentiation (p = 0.002) were significant. Potentials of current radiotherapy regimes are limited. Therefore, maximal initial treatment is warranted. In the event of a relapse after initial radical surgery, one should opt for either more aggressive standard therapy, or either new combined modalities approaches should be studied.

Incompletely resected rectum, recto-sigmoid, or sigmoid carcinoma: Results of postoperative radiotherapy and prognostic factors

Postoperative radiotherapy was given in 40 patients with gross or microscopic pathologically proven residual disease after surgical resection of rectum, recto-sigmoid, or sigmoid carcinoma. The radiotherapy target volume included the pelvis with (9 patients) or without (31 patients) the perineum. Median total dose of radiation was 50 Gy (range 30-60). One patient received 30 Gy, 10 received greater than 30 to 40 Gy, 13 received greater than 40 to 50 Gy, and 16 patients received greater than 50 to 60 Gy. The median follow-up in the survivors (16 patients) was 53 months (range: 16-85). Probability of survival with censoring for death due to intercurrent disease was 36% at 5 years. Survival for patients with microscopic residual disease (21 patients) was 40% at 5 years compared to 12% for those with gross residual disease (19 patients) (p = 0.09). Twenty-five patients relapsed. All but one relapse occurred earlier than 50 months after radiotherapy. Approximately half (12/25) of the relapses were observed within 6 months after radiotherapy. Local relapse inside the radiotherapy portals was observed in 9/40 (22%) patients. Therapy-related urogenital complications occurred in no patient and gastro-intestinal complications in three patients (7%). In one patient they were scored WHO grade 4 and in two patients WHO grade 3. Prognostic factors were analyzed using the Cox proportional hazards model. For survival differentiation, grade (p less than 0.001), stage (p = 0.04), and perineal irradiation (p = 0.03) were independent prognostic factors. With relapse-free survival as the endpoint, only stage (p = 0.003) was a statistically significant prognostic factor. There was a trend toward a better relapse-free survival when the perineum was included in the radiation portals (p = 0.09).

T1 AND T2 carcinoma of the urinary bladder: Long term result with external, preoperative, or interstitial radiotherapy

Between January 1974 and December 1984, 273 consecutive patients with cancer of the urinary bladder, Stages T1 or T2, any N, M0, were referred to the radiotherapy department of the Catharina Hospital at Eindhoven, The Netherlands and 265 were treated in a non-randomized fashion according to one of the three following schedules: 137 patients (67 T1, 70 T2) received radiotherapy only; 96 (44 T1, 52 T2) had preoperative radiotherapy followed by cystectomy and diversion according to the Bricker technique in 94/96; 32 patients (13 T1, 19 T2) had low total dose (12 Gy median) external radiotherapy followed by an interstitial cesium implant. The external radiotherapy fields included the pelvic structures. Total dose was 64 Gy median in the radiotherapy-only group and 40 Gy median in the preoperative irradiated group. The median follow-up in survivors was 81 months (range: 15-203). Locoregional relapse was observed in 50% in the group treated by external radiotherapy alone versus 17% in the group treated by preoperative radiation plus surgery and 28% of the patients who received cesium implant. During follow-up, 106/137 (77%), 67/96 (70%) and 13/32 (41%) patients died. In the radiotherapy-alone group, 38 died from intercurrent diseases, 36 from bladder cancer, two from therapy-related complications and cause of death was unknown in 30 patients. In the preoperative radiation group, the figures were 17 for intercurrent deaths, 26 related to progressive bladder cancer, 14 died due to perioperative complications and cause of death was unknown in 10. Cause of death was intercurrent in six and due to bladder cancer in seven patients treated by cesium implant. Probability of survival (calculated from the date of histological diagnosis) for the whole group, with censoring death to intercurrent disease was 53% at 5 years (56% for T1; 51% for T2) and 41% (40% for T1; 43% for T2) at 10 years. No significant difference was observed between T1 and T2 (p = 0.76). Survival in the treatment subgroups was, for patients treated by external radiotherapy only: 50% at 5 years and 33% at 10 years; for patients treated by external radiotherapy and surgery: 49% at 5 years and 42% at 10 years; for patients treated by cesium implant: 76% at 5 years and 76% at 10 years. Survival of patients in the cesium implant group was significantly better than in the other groups (p = 0.0001). Following variables were analyzed using the Cox proportional hazards model: age, gender, T1 or T2 stage, grade, cesium implant or not, and surgery or not.(ABSTRACT TRUNCATED AT 400 WORDS)

Adjuvant postoperative radiotherapy for adenocarcinoma of the rectum and rectosigmoid. A retrospective analysis of locoregional control, survival, and prognostic factors on 178 patients.

Results arc presented of a retrospective study on 178 patients receiving adjuvant postoperative radiotherapy after curative surgery for adenocarcinoma of the rectum and rectosigmoid. Tumorstages according to Gunderson-Sosin were B2: 67, B3: 5, C1: 9, C2: 94, and C3: 3. Median total dosage was 50 Gy (range: 10–66 Gy), with a median dose per fraction of 2.0 Gy, 5 fractions per week. The censored overall 5-year survival rate was 42%, and 5-year disease-free survival rate was 37%. The respective rates for stage B2 patients (n = 67) were 59% and 53%, and for stage C2 patients (n = 94), 25% and 25%. Recurrences occurred in 89% within 3 years, 8% in the fourth, and 1% in the fifth year of follow-up. Five-year local relapse rates were 27% for the stage B2 tumors and 40% for the stage C2 tumors. For survival, stage (P = .006), grade (P = .02), fixation at surgery (P = .03), and gender (P = .03) were independent prognostic factors. With local relapse-free probability (LRFP) as endpoint, grade (P < .02) was an independent prognostic factor. Dose of radiation was not of prognostic significance, neither for survival (P = .63) nor for LRFP (P = .61). Since improvement should be made in locoregional control, initiatives are taken to start preoperative radiotherapy; furthermore, the key role of surgery is emphasized.

Changing attitudes towards breast-conserving treatment of early breast cancer in the south-eastern Netherlands : results of a survey among surgeons and a registry-based analysis of patterns of care

To see whether personal preferences of surgeons can explain the trends in the use of breast-conserving therapy (BCT) of early breast cancer, questionnaires were sent to the surgeons of seven community hospitals in the south-eastern Netherlands in 1987 and 1995. The answers were set against the actual use of breast-conserving therapy in the hospitals in the period 1984-94, as monitored by the Eindhoven Cancer Registry. The proportion of surgeons who were willing to use BCT for tumours < or =3 cm increased from 43% in 1987 to 93% in 1995. In 1995, the majority of the surgeons considered multicentric tumour growth, diffuse microcalcifications on the mammogram and an extensive intraductal component around the tumour as contraindications for breast-conserving therapy. The proportion of patients with an operable, non-metastasized breast tumour of < or =5 cm in diameter undergoing breast-conservative surgery increased from 31% in 1984 to 60% in 1989 (P<0.01) and remained at that level in 1990 and 1991. Between 1991 and 1993, the proportion receiving breast-conservative surgery decreased significantly for patients younger than 50 years and a tumour 2.1-3.0cm in diameter, and also for those 50-69 years old with a tumour < or =2.0cm or 3.1-5.0cm across. The observed decrease in BCT in the south-eastern Netherlands in some subgroups seems to reflect the growing awareness of potential risk factors for local recurrence following BCT.