Significant Locoregional Control Research Articles

Stereotactic Body Radiation Therapy (SBRT) With or Without Daily Systemic Therapy for Re-Irradiation of Unresectable, Recurrent, Head and Neck Squamous Cell Carcinoma

Patients with unresectable, previously irradiated recurrent/second primary head and neck squamous cell cancers (SCC) have limited therapeutic options. Stereotactic body radiotherapy (SBRT) may overcome this inherent radioresistance, and radiosensitizing systemic therapy may further enhance RT effect. In this analysis we compared the outcomes of patients who received concurrent systemic therapy to a historical cohort to evaluate oncologic outcomes.Eligible patients had recurrent or second primary squamous cell carcinoma of the head and neck who were previously irradiated, ≥6-month interval prior to SBRT, and deemed unfit/unresectable or refused surgery. Patients were treated with SBRT to 30-40 Gy for five fractions every other day. Kaplan-Meier log-rank and Cox-proportional regression hazards analysis was performed to evaluate patient/disease factors predictive of locoregional control (LRC), and overall survival (OS), measured from the end of SBRT.A total of 63 patients met the inclusion criteria; seventeen patients enrolled on the phase 1 trial received cisplatin 15 mg/m2 prior to each fraction, and 3 patients received concurrent weekly cetuximab. The remainder of patients did not receive concurrent chemotherapy. The majority of cases were recurrences (n = 45, 71.4%). SBRT dose was 30-40 Gy (median 40 Gy). Median follow-up of the entire cohort was 6.6 months (range). One year LRC was 43.4% for patients receiving systemic therapy and 68.7% for the historical cohort (P = 0.14), and 1 year OS was 32.9% and 44.1%, respectively (P = 0.39). The addition of systemic therapy was not associated with a significant LRC or OS benefit on univariate or multivariate analysis (HR 0.80, 95% CI 0.29-2.2, P = 0.67). Gross tumor volume (GTV) ≤10 cc was significantly associated with improved LRC on univariate analysis (HR 0.31, 95% CI 0.12-0.81, P = 0.02) and trended toward significance on multivariate analysis (HR 0.3695% CI 0.13-1.02 P = 0.06). GTV≤10 cc was significantly associated with improved OS on both UVA (HR 0.27 95% CI 0.13-0.57, P < 0.01) and MVA (HR 0.20 95% CI 0.09-0.49, P < 0.01).Systemic therapy with SBRT did not appear to improve LRC or OS over SBRT alone for in the re-irradiation setting of patients with recurrent or second primary squamous cell carcinomas. We found that small tumors (GTV ≤10 cc) may be better suited for SBRT compared to larger ones (GTV > 10 cc).

Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis

PurposeTo use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM). Patients and methodsWe enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis. ResultsAfter multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P < 0.0001) and 0.58 (0.47–0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2–4 (ypT3–4) and postchemotherapy pathologic nodal stages N2–3 (ypN2–3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38–0.69, P < 0.0001), 0.60 (0.40–0.88, P = 0.0096), and 0.64 (0.48–0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0–4, ypN0–3, and pathologic American Joint Committee on Cancer stages pCR to IIIC. ConclusionFor patients with breast cancer ypT3–4, ypN2–3, or pathologic stages IIIA–IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.

‘Doing as little as possible and as much as necessary’ – Oncological efficacy of marginal mandibulectomy in resection of oral cavity cancers

BackgroundIn carefully selected oral cavity cancers, marginal mandibulectomy is an adequate procedure which achieves good disease control adhering to the principle of “doing as little as possible and as much as necessary”. MethodologyThis was a retrospective study done by reviewing the medical records of all patients who underwent marginal mandibulectomy for resection of oral cavity cancers in our institution during a period of 5 years. Data was collected from medical case records and analyzed. Results125 cases underwent marginal mandibulectomy for resection of oral cavity cancers. 88.5% of advanced oral cavity cancers that underwent neoadjuvant chemotherapy followed by marginal mandibulectomy are still disease free. The local recurrence rate was 10.4%. Among cases which recurred, 61.5% were in T2 stage of the disease and 30.8% recurred in buccal mucosa. For lesions on the mandible (26/125), the final histopathology showed bone infiltration in only 12% cases and among them only one recurred. Among 88/125 cases where the lesion was abutting mandible even after stretching mucosa, recurrence was noted only in 11.4% with 3-year overall survival of 79.3%. ConclusionsThe low recurrence rate following marginal mandibulectomy in our study shows good locoregional control when performed for a lesion close to or abutting alveolar periosteum. In management of advanced oral cavity cancers, neoadjuvant chemotherapy followed by marginal mandibulectomy was effective in achieving significant locoregional control. For superficial lesions on the mandible, marginal mandibulectomy gives adequate margin clearance resulting in long term survival.

Benefits from adjuvant intraoperative radiotherapy treatment for gastric cancer: A meta-analysis.

The benefits of adjuvant intraoperative radiotherapy (IORT) for resectable gastric cancer have been extensively studied, but data on the survival rate remains equivocal. A meta-analysis was performed of the studies involving the use of IORT for resectable gastric cancer using web-based databases. Hazard ratios (HRs) describing the impact of adjuvant IORT on the overall survival (OS) rate and locoregional control were extracted directly from the original studies or calculated from survival curves. A meta-analysis of four studies that provided OS data revealed that IORT had no significant impact on OS [HR, 0.97; 95% confidence interval (CI), 0.75-1.26; P=0.837]. In the three studies testing the efficacy of IORT for OS in the subgroup of patients with stage III disease, there was a significantly improved OS (HR, 0.60; 95% CI, 0.40-0.89; P=0.011). Significant locoregional control improvement was observed in the four studies that provided locoregional control data (HR 0.40; 95% CI, 0.26-0.62; P<0.001). This meta-analysis showed a statistically significant locoregional control benefit with the addition of IORT in patients with resectable gastric cancer. In addition, the available data revealed that adjuvant IORT may provide promising results on the survival rate for the subgroup of patients with stage III disease. Further study is required to optimize the implementation of adjuvant IORT for gastric cancer with regard to patient selection and integration with systemic therapy.

Thymoma: Clinical experience from a tertiary care institute from North India

Thymomas are the most common tumors of the mediastinum. They have varied presentation ranging from asymptomatic incidental mediastinal masses to locally extensive tumor with compressive symptoms and distant metastases. The authors present our institute's experience in combined modality management of thymomas. We retrospectively reviewed 36 patients of thymoma treated in our institute from January 2004 to December 2010. Clinical characteristics and treatment modality in form of surgery, radiotherapy (RT) and chemotherapy (CCT) were noted. Statistical analysis was done with regard to progression free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. A total of 17 patients had associated Myasthenia gravis and 3 patients had associated Cushing syndrome. Masaoka Stage 4a was the most common stage (13 patients) followed by stage 3 (10 patients), stage 2 (9 patients) and stage 1 (4 patients). Twenty seven patients underwent primary surgery, out of which 20 received adjuvant RT and five received both RT and CCT. Of nine non-surgical cases, four received only palliative RT whereas 5 received systemic CCT followed by local mediastinal RT. Overall, 23 patients had complete response while 13 had partial response. 1 patient had local recurrence. Three year PFS was 60% and 3 year OS was 83%. Most common presentation in our series was locally advanced tumors. Most of these patients require adjuvant mediastinal radiation, which helps in significant loco-regional control. Systemic CCT benefits in inoperable, advanced and high-risk tumors. Risk-adapted and multimodality approach is the need of the hour to achieve good control rates while minimizing treatment related toxicity.

Survival and failure outcomes in locally advanced esthesioneuroblastoma: a single centre experience of 15 patients

Esthesioneuroblastoma (ENB) constitutes 3 % of all malignant intranasal tumors. As the tumor is very rare, the number of patients of ENB treated in individual departments is small. We present our institute's experience in combined modality management of 15 successive patients of ENB treated from 2006 to 2010. Clinical characteristics and treatment modality in form of surgery, radiotherapy and chemotherapy were noted. Kadish stage C was the most common stage (12 patients) followed by stage B (3 patients). Fourteen patients underwent primary surgery, of which nine had total excision and five had subtotal excision. One patient was treated with combination of chemotherapy (CT) and radiotherapy (RT). Median RT dose delivered was 54 Gy. Twelve patients received CT with cisplatin and etoposide. Overall, eight patients had complete response, five had partial response, while one had static disease and progressive disease each. Two patients had distant metastases. Four-year loco-regional control (LRC) was 25 % and 4-year overall survival (OS) was 45 %. Most common presentation in our series was locally advanced tumors. Most of these patients require adjuvant RT, which helps in significant LRC. Systemic CT benefits in inoperable, advanced and high risk tumors. Risk-adapted and multimodality approach is the need of hour to achieve good control rates while minimizing treatment related toxicity.

External Pelvic and Vaginal Irradiation Versus Vaginal Irradiation Alone as Postoperative Therapy in Medium-Risk Endometrial Carcinoma: A Prospective, Randomized Study—Quality-of-Life Analysis

A combination of vaginal brachytherapy and external beam radiotherapy was compared with brachytherapy alone in medium-risk endometrial carcinomas. Quality-of-life analysis is an important part of a randomized study to find out the optimal adjuvant treatment for this group of patients. To evaluate the value of adjuvant external beam pelvic radiotherapy in adjunct to vaginal brachytherapy in medium-risk endometrial carcinoma. Quality-of-life evaluation is the main topic of this report. A consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study end points were locoregional recurrences and overall survival. Secondary end points were recurrence-free survival, toxicity, and quality-of-life. European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OV28 modules were used to evaluate global health status, functional scales, and symptom scales. Five-year locoregional relapse rates were 1.5% after external beam (ERT) plus vaginal irradiation (VBT) and 5% after vaginal irradiation alone (P = 0.013), and 5-year overall survival (OS) rates were 89% and 90%, respectively. External beam radiotherapy was associated with a higher rate of adverse effects from the intestine and the bladder, and quality-of-life parameters deteriorated at the end of radiotherapy but recovered to normal levels within a few months. There was a significant difference in favor of VBT alone with regard to adverse effects of the bowel and urinary tract, and quality-of-life. Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded; but increased late toxicity from the intestine and the bladder. External beam irradiation decreased global health status during and after treatment, and 3 functional scale items (physical, role, and social). Six of 11 symptom items showed a pattern favoring vaginal brachytherapy alone.

External Pelvic and Vaginal Irradiation Versus Vaginal Irradiation Alone as Postoperative Therapy in Medium-Risk Endometrial Carcinoma—A Prospective Randomized Study

To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity. Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity. Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-year overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone. Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases.

Breast Cancer Management: Present Scenario

The treatment management of breast cancer is perhaps the most controversial of all and has evolved a sea change over the years. Contrast enhanced MRI imaging is emerging as the most efficient imaging diagnostic tool. Newer approaches for the biopsy of inoperable breast cancer are aimed at obtaining diagnostically adequate tissue samples while minimizing invasiveness and the risk of complications. The regional vigour that Halsted followed rigorously, albeit, achieved significant locoregional control, could not lead to improved long-term survival. With the passage of time, people have understood the systemic nature of the disease and the paramount need to incorporate systemic treatment even in relatively earlier stages and curtain surgical ablative techniques. The role of primary systemic therapy in the management of breast cancer is fast emerging as a vital option. In HER 2/neu gene overexpressed patients, addition of trastuzumab to the systemic treatment is a distinct improvement in overall survival. (Med J Indones 2007; 16:55-60) Keywords: breast cancer, tumour, chemotherapy, radiotherapy, systemic therapy

Sinonasal undifferentiated carcinoma: an update

Sinonasal undifferentiated carcinoma is a rare and extremely malignant tumor of the paranasal sinuses. Historically, treatment outcomes have been poor. This review presents recent data on the management of sinonasal undifferentiated carcinoma and examines treatment trends that may result in improved locoregional control and survival. Patients who receive aggressive multimodality treatments have improved outcomes. In particular, a chemoradiotherapy regimen including concurrent platinum-based chemotherapy given preoperatively or postoperatively to patients with resectable disease seems to result in better disease-free survival. Neoadjuvant chemotherapy, although strongly advocated by some, is currently not offered by many. Although surgery seems to be an important part of the treatment for sinonasal undifferentiated carcinoma, its ideal timing, either upfront or after radiotherapy, remains uncertain. Overall, outcomes for sinonasal undifferentiated carcinoma are poor. An aggressive approach using surgery, platinum-based chemotherapy, and radiation seems to offer the greatest chance for significant locoregional control and survival.

Postoperative radiotherapy for Stage 1 endometrial carcinoma: Long-term outcome of the randomized PORTEC trial with central pathology review

In 2000, the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial were published. This trial included 714 Stage I endometrial carcinoma patients randomly assigned to postoperative pelvic radiotherapy (RT) or no further treatment, excluding those with Stage IC, Grade 3, or Stage IB, Grade 1 lesions. Radiotherapy significantly decreased the risk of locoregional recurrence (4% vs. 14%), without affecting overall survival. In this report the long-term outcome and results with central pathology review are presented. The slides of 569 patients (80%) could be obtained for pathology review. Median follow-up for patients alive was 97 months. Analysis was done according to the intention-to-treat principle. The primary study endpoints were locoregional recurrence and death. Ten-year locoregional relapse rates were 5% (RT) and 14% (controls; p < 0.0001), and 10-year overall survival was 66% and 73%, respectively (p = 0.09). Endometrial cancer related death rates were 11% (RT) and 9% (controls; p = 0.47). Pathology review showed a substantial shift from Grade 2 to Grade 1, but no significant difference for Grade 3. When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis, the results remained essentially the same, with 10-year locoregional recurrence rates of 5% (RT) and 17% (controls; p < 0.0001). In view of the significant locoregional control benefit, radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse.