Eric Berthelet

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes

Adjuvant therapy for women with T1–T2 breast carcinoma and 1–3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes.

Testosterone recovery following prolonged adjuvant androgen ablation for prostate carcinoma

This study was conducted to describe the rate and completeness of the recovery of testosterone production following prolonged temporary androgen ablative therapy in men with prostate carcinoma undergoing curative radiation therapy.

The effects of age and comorbidity on treatment and outcomes in women with endometrial cancer.

Background:Although the incidence of endometrial cancer increases with age, the effect of patient age on treatment selection and outcomes is unclear. In addition, although aging is associated with increased prevalence of comorbid conditions, the extent to which comorbidities influence endometrial cancer management is not well documented. Methods:This population-based analysis evaluates the effect of age and comorbidity on endometrial cancer treatment and outcome in a cohort of 401 patients referred to the Vancouver Island Centre, British Columbia Cancer Agency from 1989 to 1996. Treatment and 5-year actuarial overall survival (OS) and disease-free survival (DFS) were compared by age at diagnosis (<65, 65–74, and ≥75 years) and comorbidity index (Charlson score 0–1 and ≥2). Results:Median follow-up time was 7.8 years. In this cohort, 148 (37%), 152 (38%), and 101 (25%) were aged <65, 65–74, and ≥75 years, respectively. Charlson comorbidity scores ≥2 were found in 18% of patients. Distributions of disease stage, tumor characteristics, and surgical therapy were similar across age and comorbidity subgroups. Standard surgery in this cohort comprised hysterectomy without routine lymphadenectomy. In stage Ic disease, the use of postoperative RT declined with advanced age (96%, 97%, and 74% in patients aged <65, 65–74, and ≥75 years, respectively, P = 0.05) and with increased comorbidities (91% and 79% in patients with Charlson score 0–1 and ≥2, respectively, P = 0.07). Among stage Ic patients aged ≥75 years, pelvic/vaginal relapse occurred in 2 of 6 patients treated with hysterectomy alone compared with 0 of 20 patients treated with postoperative radiotherapy (P = 0.006). On multivariable Cox modeling, age at diagnosis, performance status, stage, grade, lymphovascular invasion, surgery, and radiotherapy use, but not Charlson comorbidity score, were significant predictors for overall survival. Conclusions:Although surgical therapy for endometrial cancer was not influenced by age or comorbidities, reduced use of postoperative radiotherapy in stage Ic disease was observed among women with advanced age and high comorbidity index. The associated pelvic/vaginal relapse rates were higher in elderly patients not treated with radiotherapy. Chronologic age alone should not preclude patients from consideration of optimal local therapy.

A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer

OBJECTIVE Postoperative radiotherapy is frequently employed among breast cancer patients with positive surgical margins after mastectomy but there is little evidence to support this practice. This study examined relapse and survival among women with node-negative breast cancer and positive surgical margins after mastectomy. METHODS Among 2570 women diagnosed between 1989 and 1998 and referred to the British Columbia Cancer Agency with pathologic (p)T1-2, pN0 invasive breast cancer treated with mastectomy, 94 had positive surgical margins and formed the study cohort. Women with more established indications for postmastectomy radiotherapy (PMRT) including T3-4 tumors or node-positive disease were excluded. Demographic, tumor, and treatment factors; relapse patterns; and Kaplan-Meier 8-year locoregional relapse-free, breast cancer-specific, and overall survival rates were compared between women who were treated with (n = 41) and without (n = 53) PMRT. RESULTS Median follow-up time was 7.7 years. The distributions of age, histologic grade, lymphovascular invasion (LVI), estrogen receptor status, and number of axillary nodes removed were similar between the two treatment groups. Six local chest wall recurrences (6.4%), 4 regional recurrences (4.3%), and 11 distant recurrences (11.7%) were identified. Local relapse rates were 2.4% vs. 9.4% (p = 0.23), and regional relapse rates were 2.4% vs. 5.7% (p = 0.63), with and without PMRT, respectively. Trends for higher cumulative locoregional relapse (LRR) rates without PMRT were identified in the presence of age <==50 years (LRR 20% without vs. 0% with PMRT), T2 tumor size (19.2% vs. 6.9%), grade III disease (23.1% vs. 6.7%), and LVI (16.7% vs. 9.1%). Statistical significance was not demonstrated in these differences (p > 0.10), possibly because of the small number of events. In patients with age >50 years, T1 tumors, grade I/II disease, and absence of LVI, no locoregional relapse occurred even with positive margins. PMRT did not improve distant relapse, 8-year breast cancer-specific and overall survival rates. CONCLUSION This study suggests that not all patients with node-negative breast cancer with positive margins after mastectomy require radiotherapy. Locoregional failure rates approximating 20% were observed in women with positive margins plus at least one of the following factors: age <==50 years, T2 tumor size, grade III histology, or LVI. The absolute and relative improvements in locoregional control with radiotherapy in these situations support the judicious, but not routine, use of PMRT for positive margins after mastectomy in patients with node-negative breast cancer.

Outcomes in patients with primary breast cancer and a subsequent diagnosis of endometrial cancer : Comparison of cohorts treated with and without tamoxifen

The study compared tumor characteristics and survival in women with breast cancer who subsequently developed endometrial cancer with or without a history of tamoxifen use.

Preliminary reliability and validity testing of a new Skin Toxicity Assessment Tool (STAT) in breast cancer patients undergoing radiotherapy.

Clear consensus on the clinical evaluation of acute skin toxicity among cancer patients undergoing radical radiotherapy (RT) is currently lacking. This study investigates the reliability and validity of a new Skin Toxicity Assessment Tool (STAT) to evaluate the objective and subjective manifestations of RT-induced acute skin effects. The STAT was designed by a multidisciplinary team involved in the management of radiation skin reactions. The tool has 3 components: patient and treatment parameters, observer scoring, and patient-reported symptoms, and was piloted in a cohort of 27 breast cancer patients by pairs of independent blinded observers. Each patient was assessed weekly during RT and 2 weeks after therapy completion. Validity and reliability testing of the STAT was performed. Information on the tools ease of use was obtained by recording the time necessary to complete the assessment at each visit and by a survey among the tools users. All subjects developed some degree of skin reaction during breast RT. The level of agreement between observers in eliciting subjective complaints ranged from 72% to 92% (95% CI = 63–96%; &kgr; = 0.33–0.68). The interobserver agreement in scoring skin reactions ranged from 65.0 to 97.5% (&kgr; = 0.46–0.81). Objective and subjective toxicity scores were significantly correlated (P < 0.05). The STAT was easy to use and required on average a few minutes to complete at each visit. The STAT is an easy-to-use, standardized instrument to evaluate acute skin reaction and may be applied to clinical care and research in patients undergoing radiotherapy.

Effect of bladder filling on doses to prostate and organs at risk: a treatment planning study

In the present study, we aimed to evaluate effects of bladder filling on dose–volume distributions for bladder, rectum, planning target volume (PTV), and prostate in radiation therapy of prostate cancer. Patients (n=21) were scanned with a full bladder, and after 1 hour, having been allowed to void, with an empty bladder. Radiotherapy plans were generated using a four‐field box technique and dose of 70 Gy in 35 fractions. First, plans obtained for full‐ and empty‐bladder scans were compared. Second, situations in which a patient was planned on full bladder but was treated on empty bladder, and vice versa, were simulated, assuming that patients were aligned to external tattoos. Doses to the prostate [equivalent uniform dose (EUD)], bladder and rectum [effective dose (Deff)], and normal tissue complication probability (NTCP) were compared. Dose to the small bowel was examined. Mean bladder volume was 354.3 cm3 when full and 118.2 cm3 when empty. Median prostate EUD was 70 Gy for plans based on full‐ and empty‐bladder scans alike. The median rectal Deff was 55.6 Gy for full‐bladder anatomy and 56.8 Gy for empty‐bladder anatomy, and the corresponding bladder Deff was 29.0 Gy and 49.3 Gy respectively. In 1 patient, part of the small bowel (7.5 cm3) received more than 50 Gy with full‐bladder anatomy, and in 6 patients, part (2.5 cm3−30 cm3) received more than 50 Gy with empty‐bladder anatomy. Bladder filling had no significant impact on prostate EUD or rectal Deff. A minimal volume of the small bowel received more than 50 Gy in both groups, which is below dose tolerance. The bladder Deff was higher with empty‐bladder anatomy; however, the predicted complication rates were clinically insignificant. When the multileaf collimator pattern was applied in reverse, substantial underdosing of the planning target volume (PTV) was observed, particularly for patients with prostate shifts in excess of 0.5 cm in any one direction. However, the prostate shifts showed no correlation with bladder filling, and therefore the PTV underdosing also cannot be related to bladder filling. For some patients, bladder dose–volume constraints were not fulfilled in the worst‐case scenario—that is, when a patient planned with full bladder consistently arrived for treatment with an empty bladder. PACS numbers: 87.53.‐j, 87.53.Kn, 87.53.Tf

Endoscopic response predicts for survival and organ preservation after primary chemoradiotherapy for esophageal cancer

PURPOSE To determine the role of endoscopic surveillance in predicting organ preservation and survival after primary chemoradiotherapy (CRT) for esophageal cancer. MATERIALS AND METHODS Fifty-six consecutive patients with nonmetastatic esophageal cancer were treated with primary CRT between May 1993 and April 1999 with curative intent and subsequent surveillance with endoscopy and CT scans. Patients with residual disease on endoscopy and/or CT 6 weeks after CRT were considered for immediate esophagectomy. The remaining patients continued endoscopic surveillance and were considered for esophagectomy only when local relapse was detected. Five-year survival was estimated using the Kaplan-Meier method, and univariate and multivariate analyses were performed to identify significant factors associated with disease-specific survival. RESULTS With a median follow-up of 62 months, the 5-year overall and disease-specific survival was 30% (95% confidence interval [CI]: 17%-43%) and 37% (95% CI: 22%-50%), respectively. Fourteen of 24 (58%) patients who survived more than 2 years did not require an esophagectomy. On univariate analysis, favorable prognostic factors for disease-specific survival were female gender (p = 0.026), CT-defined N(0) status (p = 0.027), and negative endoscopy at 6 weeks after CRT (p < 0.0001). On multivariate analysis, N(0) status and negative endoscopy after CRT remained significant (p = 0.03 and p < 0.0001, respectively) for disease-specific survival. On multivariate analysis for overall survival, female gender and negative endoscopy were significant (p = 0.35 and p < 0.001, respectively). The hazard ratios for disease-specific survival with positive nodal status and positive endoscopy were 2.44 (95% CI: 1.14-5.3) and 5.18 (95% CI: 2.3-11.6), respectively. CONCLUSIONS Endoscopic response after primary CRT for esophageal cancer was the most significant predictive factor for overall and disease-specific survival. Regular endoscopic surveillance after CRT achieved survival rates comparable to other strategies and successfully preserved the esophagus in the majority of patients who survived more than 2 years.

Computed tomography determination of prostate volume and maximum dimensions: a study of interobserver variability

OBJECTIVE (1) To evaluate the reproducibility of prostate volume, maximum dimensions and geometrical center coordinates determination using computed tomography (CT) and (2) to identify patterns of interobserver variability. MATERIALS AND METHODS Forty patients, suitable for our brachytherapy program, were selected for the study. All patients underwent CT scanning and the prostate volumes were determined by three radiation oncologists. Measurements of geometrical center coordinates, maximum organ dimensions in the anterior-posterior (AP), lateral (Lat) and longitudinal (Long) axes as well as prostate volumes were recorded. This yielded 840 measurements of seven variables for analysis. The means and corresponding standard deviations (SD) of each variable were calculated for each patient. The SDs were then averaged and presented as indices of dispersion. Average variations from the mean were also calculated for each observer along with the SDs. RESULTS Analysis of the geometrical center coordinates revealed acceptable variability amongst observers. For the AP, Lat and Long coordinates the SDs were 0.78, 0.89 and 1.72 mm, respectively. The corresponding values for the maximum organ dimensions were 2.54, 2.72 and 4.43 mm, respectively. While the volumes outlined by observer B were less than or equal to the mean in 95% of cases and those of observer C were greater than or equal to the mean in 93% of cases, the volumes of observer A were equally distributed above and below the mean (48% in both cases). CONCLUSION The determination of the geometrical center coordinates was reproducible amongst observers. The largest variations were seen with the Long axis. The volume determination is more variable. However, a characteristic trend was seen amongst observers when their volumes were compared to the mean volumes of the group.

Prognostic significance of blood transfusions in patients with esophageal cancer treated with combined chemoradiotherapy

Objective:Anemia occurs commonly in patients with esophageal cancer. This study evaluates the effect of blood transfusion on survival outcomes in patients with esophageal cancer treated with combined chemoradiotherapy (CRT). Patients and Methods:Fifty-six consecutive patients with unresectable esophageal cancer received 50 Gy in 25 fractions over 5 weeks concurrent with cycles 2 and 3 of cisplatin and 5-fluorouracil chemotherapy. Data on hemoglobin before and during radiation therapy (RT) and blood transfusion use were abstracted by chart review. Each patient had a blood count before every chemotherapy cycle, and the test was repeated if the blood count was low. Five-year Kaplan–Meier overall survival (OS) and relapse-free survival (RFS) estimates were compared according to pre-RT hemoglobin levels and transfusion use. Multivariate analysis using Cox regression modeling was performed to determine the prognostic significance of pre-RT hemoglobin and transfusion use on survival outcomes. Results:The 5-year OS and RFS rates were 30% and 37%, respectively. Seventeen patients (30%) received transfusions during CRT. Among 18 patients (32%) with a hemoglobin of ≤12 g/dL at the start of RT, 9 received transfusions. Pre-RT hemoglobin levels of ≤12 g/dL were strongly associated with the use of blood transfusions (P = 0.03). Five-year Kaplan–Meier OS was 65% versus 21% in patients treated with, versus without, a transfusion (P = 0.006). On multivariate analysis, the use of blood transfusion was associated with improved OS (hazard ratio, 0.26; 95% confidence interval, 0.09–0.75, P = 0.01). Conclusions:The use of blood transfusion is a significant treatment-related factor associated with improved survival in patients undergoing CRT for esophageal cancer.