The impact of comorbidity and stage on prognosis of Danish melanoma patients, 1987-2009: a registry-based cohort study.

BACKGROUND: Comorbid conditions may play an important role in the prognosis of melanoma patients but have received little attention. METHODS: Using data from Danish registries, we identified patients diagnosed with melanoma from 1987 to 2009. We estimated the prevalence of comorbidity and calculated mortality rate ratios and interaction risks between melanoma and comorbidity. For every melanoma patient, 10 individuals were selected for comparison. Individuals in the comparison cohort were matched to their corresponding melanoma patients on age, gender, and exact prevalent comorbidities. RESULTS: We included 23 476 patients, 81% of whom had no comorbidity. Higher prevalence of comorbidity was associated with more advanced cancer stage. The standardised mortality rate increased with increasing level of comorbidity in both cohorts and was consistently higher among melanoma patients. Melanoma and comorbidity interacted to increase the mortality rate. The highest proportional excess was seen in melanoma patients with comorbidity score 3, in whom interaction accounted for 77 deaths per 1000 person-years (40% of the total rate). We stratified by cancer stage and found that the interaction was markedly concentrated in patients with distant metastases. CONCLUSION: Interaction between melanoma and comorbidity was primarily concentrated in patients with distant metastases, which raises the possibility that comorbidity is associated with delay of melanoma diagnosis, advanced cancer stage, and less aggressive melanoma treatment.

Adjuvant therapy for pancreatic cancer: current treatment approaches and future challenges.

The past several decades have witnessed advances in the management of pancreatic cancer; however, much remains to be accomplished. Emerging techniques in the fields of surgery, RT, chemotherapy, and immunotherapy offer hope for greater locoregional control, survival, and quality of life for these patients.

The relationship between radiation fields and regional lymph nodes in carcinoma of the breast.

PURPOSE: To examine the relationships between tangential, anterior, and posterior radiation fields and regional lymph nodes, including Levels I-III axillary and supraclavicular lymph nodes. METHODS AND MATERIALS: Fifty-five patients underwent computed tomography (CT) scanning in the supine treatment position, and radiation fields were developed to treat appropriate breast and lymphatic regions. After conventional fields had been selected, Levels I-III axillary and supraclavicular lymph nodes were identified on multiple CT slices performed at 3-5-mm intervals and their depths to the anterior skin surface and the anterior-posterior separations at multiple levels were measured. RESULTS: The mean depths of the Levels I-III axillary nodes were 4.6, 5.1, and 3.6 cm, respectively. The mean depth of the supraclavicular nodes was 3.9 cm. The mean anterior-posterior separations at these levels were 15.4, 15.2, 15.2, and 14.6 cm. The mean depths of the nodes, therefore, were well anterior to the midline. In the two-field treatment group, Level I axillary nodes appeared in the tangential portals in 9/9 patients, either alone or with other lymph node groups. In the three-field group, Level I axillary nodes were in 16/16 tangential fields either alone or with level II nodes (8 patients). In 8 patients, Level III and the supraclavicular nodes were included in the anterior field and in the other 8, Levels II, III, and the supraclavicular nodes were in the anterior field. There was considerable variation in the nodal groups present in the posterior axillary boost field. No nodal groups were observed in 6 patients. CONCLUSION: There is considerable variation both in the depth of supraclavicular and axillary lymph nodes and the fields in which these nodal groups appear. To be certain that nodal groups which one plans to treat are actually treated, as well as to minimize nodal treatment when such treatment is not planned, it is recommended that before the placement of radiation fields, the nodal groups be outlined on a CT scan much as one would outline a tumor volume in other disease sites.

Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma.

PURPOSE: To determine the acute toxicity, outcome, and sphincter preservation rates in patients with clinically resectable uT3 adenocarcinoma of the rectum treated with preoperative combined modality therapy. METHODS AND MATERIALS: A total of 72 patients were treated from 12/90-7/98 with preoperative 50.4 Gy plus 2 cycles of concurrent 5-fluorouracil (5-FU) and leucovorin (LV) bolus daily x 5 followed by sharp or total mesorectal excision and 4 cycles of postoperative 5-FU and LV. RESULTS: Individual Grade 3+ toxicities during preoperative therapy included diarrhea, 11%; bowel movements, 9%; leukopenia, 18%; tenesmus, 1%; and thrombocytopenia, 1%. Total Grade 3+ toxicity was 28%. The pathologic complete response (CR) rate was 13%, and an additional 9% had a clinical CR for a total CR rate of 22%. Of the 35 patients who were judged clinically by their operating surgeon to require an abdominoperineal resection (APR) and were therefore treated with the goal of sphincter preservation, 89% were able to undergo sphincter-preserving surgery. Of the 21 patients eligible for analysis, 81% had good to excellent sphincter function. The 3-year actuarial patterns of failure were 2% local, 8% abdominal, and 13% distant. The 3-year actuarial survival was 95%. CONCLUSIONS: Our data confirm our preliminary reports of encouraging rates of acute toxicity, local control, survival, sphincter preservation and function with preoperative combined modality therapy. It is an alternative approach for the treatment of uT3 clinically resectable rectal cancer.

Prone breast radiotherapy in early-stage breast cancer: a preliminary analysis.

PURPOSE: Women with large breasts have marked dose inhomogeneity and often an inferior cosmetic outcome when treated with breast conservation compared to smaller-sized patients. We designed a prone breast board, which both minimizes breast separation and irradiated lung or heart volume. We report feasibility, cosmesis, and preliminary local control and survival for selected women with Stage 0-II breast cancer. MATERIALS AND METHODS: Fifty-six patients with clinical Stage 0-II breast cancer were treated with lumpectomy and breast irradiation utilizing a prototype prone breast board. A total of 59 breasts were treated. Indications for treatment in the prone position were large or pendulous breast size (n = 57), or a history of cardiopulmonary disease (n = 2). The median bra size was 41D (range, 34D-44EE). Cosmesis was evaluated on a 1-10 (worst-to-best) scale. RESULTS: Acute toxicity included skin erythema (80% of patients experienced Grade I or Grade II erythema), breast edema (72% of patients experienced mild edema), pruritus (20% of patients), and fatigue (20% of patients reported mild fatigue). One patient required a treatment break. The only late toxicity was related to long-term cosmesis. The mean overall cosmesis score for 53 patients was 9.37 (range, 8-10). Actuarial 3- and 5-year local control rates are 98%. Actuarial overall survival at 3 and 5 years are 98% and 94%. CONCLUSION: Our data indicate that treating selected women with prone breast radiotherapy is feasible and tolerated. The approach results in excellent cosmesis, and short-term outcome is comparable to traditional treatment techniques. This technique offers an innovative alternative to women who might not otherwise be considered candidates for breast conservation.

Sphincter preservation of leiomyosarcoma of the rectum and anus with local excision and brachytherapy.

PURPOSE: The aim of this study was to determine the outcome of patients with leiomyosarcoma of the rectum or anus treated with local excision and brachytherapy. METHODS: Eight patients with leiomyosarcoma of the rectum (7 patients) or anus (1 patient) were treated with a transanal excision followed by a temporary iridium-192 interstitial implant to 4,500 cGy. Median tumor size was 4.2 (range, 1.5-5) cm. Margins were positive in six patients, negative in one patient, and close in one patient. RESULTS: With a median follow-up of 53 months, median survival time was 53 months and the three-year actuarial survival rate was 71 percent. The cumulative incidence of failure as a component of failure for local was 25 percent (2/8), for abdominal was 0 percent (0/8), and for distant was 25 percent (2/8). Four patients eligible for functional analysis all had excellent sphincter function (1-2 bowel movements per day, no soilage). CONCLUSION: In selected patients the use of conservative surgery followed by brachytherapy is a reasonable alternative to an abdominoperineal resection. However, more experience and longer follow-up are needed before this approach can be recommended routinely.

Comparison of the 5-year outcome and morbidity of three-dimensional conformal radiotherapy versus transperineal permanent iodine-125 implantation for early-stage prostatic cancer.

PURPOSE: To compare the prostate-specific antigen (PSA) relapse-free survival outcome and incidence of late toxicity for patients with early-stage prostate cancer treated at a single institution with either three-dimensional conformal radiotherapy (3D-CRT) or transperineal permanent implantation (TPI) with iodine-125 seeds. MATERIALS AND METHODS: Patients with favorable-risk prostate cancer, defined as a pretreatment PSA of less than or equal to 10.0 ng/mL, Gleason score of 6 or lower, and stage less than or equal to T2b, were selected for this analysis. Between 1989 and 1996, 137 such patients were treated with 3D-CRT and 145 with TPI. The median ages of the 3D-CRT and TPI groups were 68 years and 64 years, respectively. The median dose of 3D-CRT was 70.2 Gy, and the median implant dose was 150 Gy. Prostate-specific antigen relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up times for the 3D-CRT and TPI groups were 36 and 24 months, respectively. RESULTS: Eleven patients (8%) in the 3D-CRT group and 12 patients (8%) in the TPI group developed a biochemical relapse. The 5-year PSA relapse-free survival rates for the 3D-CRT and the TPI groups were 88% and 82%, respectively (P = .09). Protracted grade 2 urinary symptoms were more prevalent among patients treated with TPI compared with 3D-CRT. Grade 2 urinary toxicity, which was manifest after the implant and persisted for more than 1 year after this procedure, was observed in 45 patients (31%) in the TPI group. In these 45 patients, the median duration of grade 2 urinary symptoms was 23 months (range, 12 to 70 months). On the other hand, acute grade 2 urinary symptoms resolved within 4 to 6 weeks after completion of 3D-CRT, and the 5-year actuarial likelihood of late grade 2 urinary toxicity for the 3D-CRT group was only 8%. The 5-year actuarial likelihood of developing a urethral stricture (grade 3 urinary toxicity) for the 3D-CRT and TPI groups was 2% and 12%, respectively (P<.0002). Of 45 patients who developed grade 2 or higher urinary toxicity after TPI, the likelihood of resolution or significant improvement of these symptoms at 36 months from onset was 59%. The 5-year likelihood of grade 2 late rectal toxicity for the 3D-CRT and TPI patients was similar (6% and 11%, respectively; P = .97). No patient in either group developed grade 3 or higher late rectal toxicity. The 5-year likelihood of posttreatment erectile dysfunction among patients who were initially potent before therapy was 43% for the 3D-CRT group and 53% for the TPI group (P = .52). CONCLUSION: Both 3D-CRT and TPI are associated with an excellent PSA outcome for patients with early-stage prostate cancer. Urinary toxicities are more prevalent for the TPI group and subsequently resolve or improve in most patients. In addition to evaluating long-term follow-up, future comparisons will require detailed quality-of-life assessments to further determine the impact of these toxicities on the overall well-being and quality of life of the individual patient.

Pathologic features from prostate needle biopsy and prognosis after I-125 brachytherapy.

To evaluate the role of detailed pathologic features in predicting outcome for early-stage prostate cancer treated with I-125 brachytherapy. The pretreatment biopsy slides of 103 patients with T1/T2 and Gleason scores of 4-7 prostatic carcinoma, which was treated by transperineal I-125 implantation, were reviewed retrospectively by a single pathologist (P.B.G.). Biochemical tumor control rates [prostate-specific antigen (PSA) below 1.0] were correlated with pretreatment PSA, Gleason score, the amount of tumor in the biopsy samples, and the presence of perineural invasion. In Cox proportional-hazard, multivariate analysis, the strongest predictors of failure were pretreatment PSA above 10 ng/ml (P = 0.013) and the length of the biopsy specimen replaced by tumor (P = 0.15). The percent of biopsy tissue replaced by tumor (P = 0. 74), perineural invasion (P = 0.78), and Gleason score (P = 0.66) were less predictive of prognosis. It was concluded that pretreatment PSA is the strongest predictor of biochemical failure. Detailed assessment of pathological features on needle biopsy added little prognostic information beyond that of pretreatment PSA alone. Like all other prognostic parameters for prostate cancer, there is considerable overlap in pathologic features between those patients who will or will not be controlled biochemically.

Prostate brachytherapy in patients with inflammatory bowel disease.

PURPOSE: There are minimal data to support the perceived contraindication of radiation therapy in patients with inflammatory bowel disease (IBD). Because of widespread concern about the possibility of radiation-related morbidity in IBD patients, the posttreatment course for 6 patients with a history of IBD who were treated with 125I prostate implantation for early stage prostate cancer are reported here. MATERIALS AND METHODS: Six patients with a prior history of IBD and Stage T1c-T2c prostatic carcinoma underwent 125I prostate brachytherapy from 1991-1996. Three patients had Crohn's disease and three had ulcerative colitis. The treatment plans were designed to treat the preimplant prostatic margin, as defined on planning CT scan, to 150 Gy. No special effort was made to minimize the rectal surface dose. Detailed records were available for all patients, and all patients were interviewed for this report. Follow-up ranged from 1 to 6 years (median: 3.7 years). RESULTS: None of the 6 patients experienced unusual or significant gastrointestinal side effects following implantation. All 6 patients remain free of GI complications. The rectal surface area that received > 100 Gy was kept below 10 mm2 in all patients, in accordance with previously published guidelines. CONCLUSIONS: Based on the limited information available, it appears that prostate brachytherapy is safe in patients with a history of IBD.

Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer.

PURPOSE: We report the downstaging, sphincter preservation, acute toxicity, and preliminary local control and survival results of preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and concurrent radiation therapy followed by postoperative LV/5-FU for treatment of patients with clinically resectable T3 rectal cancer. MATERIALS AND METHODS: A total of 32 patients received two monthly cycles of preoperative LV/5-FU (bolus daily X 5). Radiation therapy (5,040 cGy) began concurrently on day 1. Postoperatively, patients received a median of two monthly cycles of LV/5-FU (range, 0-10). RESULTS: The complete response rate was 9 percent pathologic and 13 percent clinical, for a total of 22 percent. Total Grade 3+ acute toxicity during the preoperative combined modality segment was 25 percent (8/32). Of the 20 patients who were thought to initially require an abdominoperineal resection and for whom the intent of treatment was sphincter preservation, 17 (85 percent) were able to undergo sphincter-preserving surgery. With a median follow-up of 22 (3-59) months, none have developed local failure, and the three-year actuarial disease-free survival rate was 60 percent. CONCLUSION: Our data reveal encouraging downstaging, sphincter preservation and acute toxicity with this regimen. Additional follow-up is needed to assess the long-term local control and survival rates.