Better Defining the Role of Total Neoadjuvant Radiation: Changing Paradigms in Locally Advanced Pancreatic Cancer.

BACKGROUND: This study was designed to better define the role of radiation (Neo-Rad) in addition to neoadjuvant multiagent chemotherapy (NAT) for the treatment of locally advanced pancreatic cancer. METHODS: Retrospective cohort study using the NCDB. Individuals with AJCC clinical T3/T4 pancreatic carcinoma who underwent resection and multiagent chemotherapy were included. Kaplan-Meier, logistic-regression, and Cox proportional-hazard models were used for analysis. RESULTS: A total of 2703 patients were included; 2039 had T3 and 664 had T4 tumors, and 1092 (40.4%) received Neo-Rad. Median follow-up was 22.5 months. During the study period, there was increased use of NAT and a decline in the use of Neo-Rad. Addition of Neo-Rad did not affect 30-day (2.51% vs. 3.24%, p = 0.272) or 90-day mortality (5.23% vs. 6.38%, p = 0.216). Neo-Rad was not associated with improved overall survival on univariable (25.95 vs. 24.7 months, p = 0.202), or multivariable analyses (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.85-1.05). Time from diagnosis to definitive surgery was increased by Neo-Rad (204 vs. 115 days, p < 0.001). Neo-Rad was associated with increased pathologic downstaging in T3 (32.8% vs. 14.4%) (odds ratio [OR] 2.90; 95% CI 2.30-3.66) and T4 tumors (88.9% vs. 77.8%) (OR 2.29; 95% CI 1.44-3.67); complete pathologic response (5.3% vs. 1.6%) (OR 2.89; 95% CI 1.73-4.83), and increased R0 resection rates (85.7% vs. 76.8%) (OR 1.79; 95% CI 1.44-2.23). CONCLUSIONS: The use of neoadjuvant therapy is increasing for the treatment of locally advanced pancreatic cancer. The addition of radiation to neoadjuvant chemotherapy is associated with improved antineoplastic effectiveness (downstaging, complete pathologic response), surgical resection (R0 rates), but has no effect on overall survival.

Locoregional treatment outcomes after multimodality management of inflammatory breast cancer.

PURPOSE: The aims of this study were to determine outcomes for patients with inflammatory breast cancer (IBC) treated with multimodality therapy, to identify factors associated with locoregional recurrence, and to determine which patients may benefit from radiation dose escalation. METHODS AND MATERIALS: We retrospectively reviewed 256 consecutive patients with nonmetastatic IBC treated at our institution between 1977 and 2004. RESULTS: The 192 patients who were able to complete the planned course of chemotherapy, mastectomy, and postmastectomy radiation had significantly better outcomes than the 64 patients who did not. The respective 5-year outcome rates were: locoregional control (84% vs. 51%), distant metastasis-free survival (47% vs. 20%), and overall survival (51% vs. 24%) (p < 0.0001 for all comparisons). Univariate factors significantly associated with locoregional control in the patients who completed plan treatment were response to neoadjuvant chemotherapy, surgical margin status, number of involved lymph nodes, and use of taxanes. Increasing the total chest-wall dose of postmastectomy radiation from 60 Gy to 66 Gy significantly improved locoregional control for patients who experienced less than a partial response to chemotherapy, patients with positive, close, or unknown margins, and patients <45 years of age. CONCLUSIONS: Patients with IBC who are able to complete treatment with chemotherapy, mastectomy, and postmastectomy radiation have a high probability of locoregional control. Escalation of postmastectomy radiation dose to 66 Gy appears to benefit patients with disease that responds poorly to chemotherapy, those with positive, close, or unknown margin status, and those <45 years of age.

Postoperative radiotherapy for maxillary sinus cancer: long-term outcomes and toxicities of treatment.

PURPOSE: To determine the effects of three changes in radiotherapy technique on the outcomes for patients irradiated postoperatively for maxillary sinus cancer. METHODS AND MATERIALS: The data of 146 patients treated between 1969 and 2002 were reviewed. The patients were separated into two groups according to the date of treatment. Group 1 included 90 patients treated before 1991 and Group 2 included 56 patients treated after 1991, when the three changes were implemented. The outcomes were compared between the two groups. RESULTS: No differences were found in the 5-year overall survival, recurrence-free survival, local control, nodal control, or distant metastasis rates between the two groups (51% vs. 62%, 51% vs. 57%, 76% vs. 70%, 82% vs. 83%, and 28% vs. 17% for Groups 1 and 2, respectively). The three changes were to increase the portals to cover the base of the skull in patients with perineural invasion, reducing their risk of local recurrence; the addition of elective neck irradiation in patients with squamous or undifferentiated histologic features, improving the nodal control, distant metastasis, and recurrence-free survival rates (64% vs. 93%, 20% vs. 3%, and 45% vs. 67%, respectively; p < 0.05 for all comparisons); and improving the dose distributions within the target volume, reducing the late Grade 3-4 complication rates (34% in Group 1 vs. 8% in Group 2, p = 0.014). Multivariate analysis revealed advancing age, the need for enucleation, and positive margins as independent predictors of worse overall survival. The need for enucleation also predicted for worse local control. CONCLUSION: The three changes in radiotherapy technique improved the outcomes for select patients as predicted. Despite these changes, little demonstrable overall improvement occurred in local control or survival for these patients and additional work must be done.

Inflammatory breast cancer: current concepts in local management.

Inflammatory breast cancer (IBC) is a very aggressive form of breast carcinoma marked by rapid disease progression and early distant dissemination. Despite this fact, nearly 70% of patients diagnosed with (IBC) will have localized disease at presentation. As survival for patients with IBC has improved with the addition and routine use of doxorubicin-based chemotherapy, local management has emerged as a critical component of the curative management of these patients. Over the last two decades, local control rates for patients with IBC have dramatically improved. Utilization of a combined-modality approach employing neoadjuvant chemotherapy followed by mastectomy and adjuvant chemotherapy with accelerated hyperfractionated radiation to 66 Gy has transformed what was once a disease with local control rates less than 50% to one with local control rates on the order of 70%-80%. In patients whose disease responds to chemotherapy, the 5-year local control rates are even higher. These improvements in local control have translated into improvements in survival. In this paper, we review many of the exciting advances in locoregional management of IBC. We analyze the relevant literature pertaining to those local treatment options, review treatment techniques, and provide evidence-based treatment recommendations fro practicing oncologists.