Adjuvant radiation therapy is associated with improved survival for gallbladder carcinoma with regional metastatic disease

BACKGROUND: Gallbladder carcinoma is a rare malignancy and is associated with dismal outcomes. The aim of this study was to better define the role of adjuvant radiation therapy in the management of gallbladder carcinoma. METHODS: The Surveillance, Epidemiological, and End Results (SEER) survey from the National Cancer Institute was queried from 1992 to 2002. Retrospective analysis was done. The end-point of the study was overall survival. RESULTS: There were a total of 3,187 cases of gallbladder carcinoma in the registry from 1992 to 2002. Of the surgical group, 35% were stage I, 36% were stage II, 6% were stage III, and 21% were stage IV. Adjuvant radiation was used in 17% of the cases. The median survival for those patients receiving adjuvant radiation therapy was 14 months compared to an 8 months median survival for those treated without adjuvant radiation therapy (P < or = 0.001). The survival benefit associated with radiation use was only presenting those patients with regional spread (P = 0.0001) and tumors infiltrating the liver (P = 0.011). CONCLUSION: The use of adjuvant radiation therapy is associated with improved survival in patients with locally advanced gallbladder cancer or gallbladder cancer with regional disease.     

A Canadian economic analysis of U.S. Oncology Adjuvant Trial 9735

Objectives

Recent results of the U.S. Oncology Adjuvant Trial 9735 demonstrated significant disease-free survival and overall survival benefits for docetaxel and cyclophosphamide (tc) compared with doxorubicin and cyclophosphamide (ac) in the adjuvant treatment of operable invasive breast cancer. Based on clinical data from the 9735 study, we evaluated the lifetime cost-effectiveness of tc compared with ac from the perspective of the Canadian publicly funded health care system.

Methods

A Markov model was developed to estimate the incremental cost per quality-adjusted life-year gained and per life-year gained. Monthly survival and risk of disease recurrence up to 7 years were obtained directly from the overall survival and disease-free survival curves in the 9735 study; life-years beyond 7 years were estimated using the average life expectancy of age-matched women in the general Canadian population. Canadian-specific resource utilization and unit costs (in 2008 Canadian dollars) were applied to estimate costs for chemotherapy administration, chemotherapy-related toxicities, recurrence, and adverse events. Health-utility scores and decrements used in the calculation of quality-adjusted life-years were derived from the literature.

Results

The lifetime cost per quality-adjusted life-year gained was $8,251 for tc compared with ac, and the cost per life-year gained was $6,842. The results were robust across a range of sensitivity analyses.

Conclusions

Cost-effectiveness, combined with efficacy and an acceptable safety profile, support the adoption of tc as an alternative to ac in Canadian clinical practice for the adjuvant treatment of operable early breast cancer.     

Good clinical response of breast cancers to neoadjuvant chemoendocrine therapy is associated with improved overall survival.

BACKGROUND: We present extended follow-up from a prospective randomised trial evaluating the role of neoadjuvant chemoendocrine therapy in the treatment of operable breast cancer. PATIENTS AND METHODS: 309 women were randomised to primary surgery followed by eight cycles of adjuvant mitoxantrone, methotrexate with tamoxifen (2MT) or 2MT with mitomycin-C (3MT) versus the same regimen for four cycles before followed by four cycles after surgery. For this analysis the median follow-up of patients was 112 months. RESULTS: After 10 years follow-up there is still no statistically significant difference in disease-free survival (DFS) (71% versus 71%) or overall survival (OS) (63% versus 70%) when comparing adjuvant versus neoadjuvant treatment, respectively. Of 144 evaluable patients in the neoadjuvant arm, 74 achieved a good clinical response and 70 patients achieved a poor clinical response. Good responders had a superior DFS (80% versus 64%, P=0.01) and OS (77% versus 63%, P=0.03) compared to poor responders. CONCLUSIONS: At 10 years, neoadjuvant and adjuvant treatment continue to have equivalent OS and DFS. Good clinical response to neoadjuvant chemotherapy is associated with superior DFS and OS. This supports the use of clinical response of primary breast cancer to neoadjuvant therapy as a surrogate marker of survival benefit.     

Sequential adjuvant chemotherapy after surgical resection of high‐risk urothelial carcinoma

BACKGROUND:

Despite definitive surgery, the survival of patients with high‐risk urothelial carcinoma (UC) is poor. Adjuvant cisplatin‐based chemotherapy may be beneficial, but it is restricted by the need for normal renal function (RF). Sequential administration of adjuvant chemotherapy facilitates drug delivery and improves survival in patients with breast cancer. The objective of this study was to evaluate the feasibility and survival impact of adjuvant, sequential chemotherapy in patients with high‐risk UC.

METHODS:

Fifty patients were treated on 2 simultaneous protocols between 1997 and 2004. The patients on Protocol A (normal RF) received doxorubicin and gemcitabine (AG) followed by paclitaxel and cisplatin. The patients on Protocol B (impaired RF) received AG followed by paclitaxel plus carboplatin. Overall survival (OS) and disease‐specific survival (DSS) were compared with a group of 203 contemporary control patients who had similar pathology and RF and who underwent surgery alone.

RESULTS:

The median follow‐up of protocol patients was 6.5 years (range, 0.9‐8.6 years), and 25 patients remained alive. The median follow‐up of the control group was 4.7 years (0.0‐9.2), and 68 patients remained alive. The median OS for patients on Protocol A was greater than that for controls who had good RF (4.6 years vs 2.5 years; P = .03). The median OS for patients on Protocol B was greater than that for controls who had impaired RF (3.4 years vs 2 years; P = .04). DSS for the protocol and matched control groups was similar (good RF: 4.6 years vs 3 years; P = .24; impaired RF: 3.4 years vs 3.3 years; P = .40).

CONCLUSIONS:

In this nonrandomized study, adjuvant, sequential chemotherapy for patients with high‐risk UC did not improve DSS over that observed with surgery alone. Cancer 2009. © 2009 American Cancer Society.     

Conditional survival and recurrence of remnant gastric cancer after surgical resection: A multi‐institutional study

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow‐up strategies. A total of 298 patients were analyzed for their 3‐year conditional overall survival (COS3), 3‐year conditional disease‐specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5‐year overall survival (OS) and the 5‐year disease‐specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%‐83.0%, Δ36.6% vs ≤T2: 82.4%‐85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time‐dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time‐dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow‐up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow‐up model for RGC patients of different stages, which may affect the design of future clinical trials.     

Palliative resection of the primary tumor is associated with improved overall survival in incurable stage IV colorectal cancer: A nationwide population‐based propensity‐score adjusted study in the Netherlands

As the value of palliative primary tumor resection in stage IV colorectal cancer (CRC) is still under debate, the purpose of this population‐based study was to investigate if palliative primary tumor resection as the initial treatment after diagnosis was associated with improved overall survival. All patients with stage IV colorectal adenocarcinoma (2008–2011) were selected from the Netherlands Cancer Registry, and patients undergoing treatment with curative intent (i.e., metastasectomy, radiofrequency ablation and/or hyperthermic intraperitoneal chemotherapy), or best supportive care were excluded. After propensity score matching, a multivariable Cox proportional hazard model was performed to determine the association between treatment strategy and mortality. From a total group of 10,371 patients with stage IV CRC, 2,746 patients (26%) underwent an elective palliative resection of the primary tumor, whether or not followed by systemic therapy, and 3,345 patients (32%) were initially treated with palliative systemic therapy. After propensity score matching, median overall survival in these groups was 17.2 months (95% CI 16.3–18.1) and 11.5 months (95% CI 11.0–12.0), respectively. In Cox regression analysis, primary tumor resection was significantly associated with improved overall survival (hazard ratio of death = 0.44 [95% CI 0.35–0.55], p < 0.001). This large population‐based study shows an overall survival benefit for patients with incurable stage IV CRC who underwent primary tumor resection as the initial treatment after diagnosis, compared to patients who started systemic therapy with the primary tumor in situ. This result is an argument in favor of resection of the primary tumor, even when patients have little to no symptoms.