The role of adjuvant radiation therapy (RT) in the treatment for early-stage hormone receptor positive and HER2 negative breast cancer in older women after breast conservation therapy remains controversial. We investigated national practice patterns and outcomes for these patients using the National Cancer Database (NCDB). Women aged 65 years and older with hormone receptor positive and HER2 negative pathologic T1-T2N0M0 measuring up to 3 cm invasive breast cancer who were treated with breast conservation and adjuvant endocrine therapy without adjuvant chemotherapy from 2006-2013 were identified and stratified by the use of adjuvant RT. Multivariable proportional hazards modelling was used to examine the association of treatment and mortality adjusting for demographic, socioeconomic and clinicopathologic factors. A total of 61,395 patients with a median follow-up of 48.7 months (range 0-107) were identified. Improved overall survival was associated with younger age, facility type, income level, lower Charlson-Deyo comorbidity index, lower stage, smaller tumor size, number of nodes examined, and receipt of adjuvant RT (all P<.05). The overall 5-year survival rate was 93.0% (95% confidence interval 92.7%-93.3%) in the adjuvant RT group and 83.6% (95% confidence interval 82.5%-84.7%) in the non-adjuvant RT group (P<.0001). Improved survival is associated with receipt of adjuvant radiation therapy for older women with early-stage hormone receptor positive HER2 negative breast cancer who received adjuvant endocrine therapy.

Objectives The utility of adjuvant external beam radiation therapy after surgery for pancreatic adenocarcinoma remains controversial. Our aim was to identify subsets of patients who may benefit from adjuvant external beam radiation therapy. Methods 6114 patients with pancreatic adenocarcinoma treated with oncologic surgery between 2004 and 2010 were extracted from the SEER database. Demographic and treatment information was obtained for these patients, including whether or not patients received adjuvant external beam radiation therapy. A Cox multivariable analysis was performed to provide an adjusted hazard ratio of dying from pancreatic cancer. Results The adjusted hazard ratio of dying from pancreatic cancer favored the adjuvant external beam radiation therapy arm (HRDPC=0.75, 95% CI 0.70-0.79, p<0.0001). Unfortunately, it was not possible to elucidate subsets of patients who may or may not share the benefit of adjuvant external beam radiation therapy based on prognostic factors or treatment approaches. Interestingly, the hazard ratio of dying from pancreatic cancer for the overall population was statistically significantly improved in 2009 and 2010 as compared to 2004. The hazard ratio of dying from pancreatic cancer did not significantly improve in the adjuvant external beam radiation therapy population with time. Discussion For the overall population in the SEER database, patients receiving adjuvant EBRT after surgery are at decreased risk of dying from pancreatic cancer.

The role of postoperative radiotherapy (PORT) in the treatment of pathologic N2 (pN2) non–small cell lung cancer (NSCLC) remains controversial. A heterogeneous set of trials and meta-analyses conducted over a long period of time have come to differing conclusions. We investigated national practice patterns for patients with pN2 NSCLC treated with surgery and multiagent chemotherapy and the impact of modern PORT on OS using the National Cancer Database (NCDB). Patients with known histologies of pN2 NSCLC who underwent surgery with negative margins and received adjuvant multiagent chemotherapy from 2004-2013 were identified from the NCDB and stratified by the use of PORT (≥45 Gy). Patients also had to have survived at least 98 days after chemotherapy initiation to be included, so that patients were only included if they were expected to survive long enough to receive adjuvant therapy. To prevent receipt of concurrent chemoradiation, patients in the PORT group received radiation ≥84 days from the initiation date of chemotherapy. Landmark analysis was set at 120 days following the initiation date of adjuvant chemotherapy to prevent survival bias in the non-PORT group, as this was the median time to initiation of PORT. Multivariable proportional hazards modelling was used to examine factors associated with receiving PORT and the association of treatment and mortality adjusting for demographic, socioeconomic and clinicopathologic factors. A total of 2,815 patients were identified with median follow-up of 32.5 months. Improved survival was associated with female sex, lower Charlson-Deyo comorbidity index, race, smaller tumor size, squamous histology, lobectomy as surgery performed and receipt of PORT. Prior to landmark analysis, the HR showed a benefit to PORT. This benefit remained after landmark analysis was completed, with a median overall survival was 51.7 months in the PORT group versus 44.2 months in the no PORT group (adjusted HR 0.82, [95% CI = 0.71 to 0.93]; P < 0.005). Factors associated with receipt of PORT were facility location, Charlson-Deyo comorbidity index and grade (all P < 0.05). Improved survival is associated with receipt of PORT for patients with N2 NSCLC treated with complete resection and multiagent chemotherapy. Evidence from randomized trials should better delineate the role of PORT in this patient population.

The median survival for patients with Glioblastoma Multiforme (GBM) remains poor. Once recurrent, treatment options include systemic agents, resection of recurrent disease, and/or additional radiation treatments. Unfortunately, re-irradiation for local recurrence increases the risk of radiation necrosis (RN). Intraoperative brachytherapy with Cs-131 minimizes the chance of exposure of normal brain tissue to RN but, in light of re-irradiation, may still cause RN. In a prospective pilot study, we performed assessment of incidence of RN in patients with recurrent GBM treated with intra-operative Cs-131 at the time of neurosurgical resection. Twenty-one patients with recurrent GBM received Cs-131 intraoperative brachytherapy to 80Gy to 0.5cm. All patients had received the standard 60Gy adjuvant radiation therapy and chemotherapy after their initial diagnosis. The median age at diagnosis was 52 years (range, 35-82 years). There were 12 males and 9 females. At recurrence, 50% of patients achieved GTR and 50% achieved a STR. Twenty of 21 patients received bevacizumab (10mg/kg) prior to Cs-131 implantation, after Cs-131 implantation, or both prior to and after implant. Patients underwent MRI scans to monitor for recurrence/progression and RN with follow-up exams about every 2 months. Median follow-up time from resection and Cs-131 brachytherapy was 10 months (range, 5-26 months). The median number of Cs-131 seeds placed was 40 (range, 20-74), with a median total activity of 87.2 U (range, 41.08-201.3 U). The median tumor size was 4.65cm (range 1.2-9 cm). Twenty-five percent of patients were alive at last follow-up. Median time to local recurrence was 5.0 months. Median time to distant recurrence was 5.1 months. Fifteen of 21 (71%) sustained local progression. There was a 0% incidence of RN. Our pilot study demonstrates that treatment with intraoperative Cs-131 brachytherapy isotope in the tumor bed is a good treatment approach for recurrent GBM with no incidence of RN. From the literature, we know that bevacizumab reduces the risk of RN. The fact that no RN occurred in any of our re-irradiated patients suggests that high conformality of brachytherapy and addition of bevacizumab is an appropriate combination to avoid this potentially serious complication. Further prospective studies are ongoing to evaluate the efficacy of Cs-131 for GBM in the recurrent setting.

Purpose/Objective(s)Cost analysis is a useful tool in justifying the adoption of new treatment strategies with better clinical outcomes. In the past, a cost-effectiveness ratio (CER) of $5084 per quality-adjusted life year (QALY) gained has been used to justify the switch from 3D-CRT to IMRT for definitive treatment of oropharyngeal cancer. A CER of $27000 per QALY gained has been used to justify the switch from 3D-CRT to IMRT for definitive treatment of prostate cancer. Definitive chemoradiation has been a standard for locally advanced (Stage III or IV, non-metastatic) tonsillar cancer, sparing the morbidity associated with traditional forms of surgery. Trans-oral robotic surgery (TORS) is a minimally invasive approach which has been explored as an alternative to definitive chemoradiation; adjuvant radiation +/- chemotherapy still plays a role for postoperative patients.Materials/MethodsThree treatment approaches for locally advanced tonsillar cancer were analyzed 1: Definitive chemoradiation (CRT) to 70 Gy in 35 fractions with 3 cycles of concurrent cisplatin, 2: TORS plus adjuvant RT, 60 Gy in 30 fractions without chemotherapy, and 3: TORS plus adjuvant chemoradiation, 60 Gy in 30 fractions with 2 cycles of cisplatin. A proportion was used to determine how many QALYs must be added by TORS to justify its cost-effectiveness using the historical CERs discussed above.ResultsAt our institution, the cost of each treatment approach was as follows- Approach 1: $139504; Approach 2: $203755; Approach 3: $223755. TORS would need to add 12.6 QALYs when comparing approach 2 to 1 to be cost-effective per the oropharyngeal cancer CER. TORS would need to add 2.4 QALYs when comparing approach 2 to 1 to be cost-effective per the prostate cancer CER. TORS would need to add 16.6 QALYs when comparing approach 3 to 1 to be cost-effective per the oropharyngeal CER. TORS would need to add 3.1 QALYs when comparing approach 3 to 1 to be cost-effective per the prostate CER.ConclusionsWe performed a cost-analysis of the use of TORS for locally advanced tonsillar cancer. Historical data was used to help determine the clinical benefit that would be necessary with TORS to justify its additional cost. TORS would need to add at least 2.4 QALYs when compared with definitive CRT to justify transition over to TORS as a cost-effective advance in treatment. Further analysis of clinical outcomes data will enable a more complete cost-effectiveness analysis. However, given the limited survival of patients with locally advanced tonsillar cancer, the likelihood that TORS will provide a cost-effective clinical benefit may be low. Purpose/Objective(s)Cost analysis is a useful tool in justifying the adoption of new treatment strategies with better clinical outcomes. In the past, a cost-effectiveness ratio (CER) of $5084 per quality-adjusted life year (QALY) gained has been used to justify the switch from 3D-CRT to IMRT for definitive treatment of oropharyngeal cancer. A CER of $27000 per QALY gained has been used to justify the switch from 3D-CRT to IMRT for definitive treatment of prostate cancer. Definitive chemoradiation has been a standard for locally advanced (Stage III or IV, non-metastatic) tonsillar cancer, sparing the morbidity associated with traditional forms of surgery. Trans-oral robotic surgery (TORS) is a minimally invasive approach which has been explored as an alternative to definitive chemoradiation; adjuvant radiation +/- chemotherapy still plays a role for postoperative patients. Cost analysis is a useful tool in justifying the adoption of new treatment strategies with better clinical outcomes. In the past, a cost-effectiveness ratio (CER) of $5084 per quality-adjusted life year (QALY) gained has been used to justify the switch from 3D-CRT to IMRT for definitive treatment of oropharyngeal cancer. A CER of $27000 per QALY gained has been used to justify the switch from 3D-CRT to IMRT for definitive treatment of prostate cancer. Definitive chemoradiation has been a standard for locally advanced (Stage III or IV, non-metastatic) tonsillar cancer, sparing the morbidity associated with traditional forms of surgery. Trans-oral robotic surgery (TORS) is a minimally invasive approach which has been explored as an alternative to definitive chemoradiation; adjuvant radiation +/- chemotherapy still plays a role for postoperative patients. Materials/MethodsThree treatment approaches for locally advanced tonsillar cancer were analyzed 1: Definitive chemoradiation (CRT) to 70 Gy in 35 fractions with 3 cycles of concurrent cisplatin, 2: TORS plus adjuvant RT, 60 Gy in 30 fractions without chemotherapy, and 3: TORS plus adjuvant chemoradiation, 60 Gy in 30 fractions with 2 cycles of cisplatin. A proportion was used to determine how many QALYs must be added by TORS to justify its cost-effectiveness using the historical CERs discussed above. Three treatment approaches for locally advanced tonsillar cancer were analyzed 1: Definitive chemoradiation (CRT) to 70 Gy in 35 fractions with 3 cycles of concurrent cisplatin, 2: TORS plus adjuvant RT, 60 Gy in 30 fractions without chemotherapy, and 3: TORS plus adjuvant chemoradiation, 60 Gy in 30 fractions with 2 cycles of cisplatin. A proportion was used to determine how many QALYs must be added by TORS to justify its cost-effectiveness using the historical CERs discussed above. ResultsAt our institution, the cost of each treatment approach was as follows- Approach 1: $139504; Approach 2: $203755; Approach 3: $223755. TORS would need to add 12.6 QALYs when comparing approach 2 to 1 to be cost-effective per the oropharyngeal cancer CER. TORS would need to add 2.4 QALYs when comparing approach 2 to 1 to be cost-effective per the prostate cancer CER. TORS would need to add 16.6 QALYs when comparing approach 3 to 1 to be cost-effective per the oropharyngeal CER. TORS would need to add 3.1 QALYs when comparing approach 3 to 1 to be cost-effective per the prostate CER. At our institution, the cost of each treatment approach was as follows- Approach 1: $139504; Approach 2: $203755; Approach 3: $223755. TORS would need to add 12.6 QALYs when comparing approach 2 to 1 to be cost-effective per the oropharyngeal cancer CER. TORS would need to add 2.4 QALYs when comparing approach 2 to 1 to be cost-effective per the prostate cancer CER. TORS would need to add 16.6 QALYs when comparing approach 3 to 1 to be cost-effective per the oropharyngeal CER. TORS would need to add 3.1 QALYs when comparing approach 3 to 1 to be cost-effective per the prostate CER. ConclusionsWe performed a cost-analysis of the use of TORS for locally advanced tonsillar cancer. Historical data was used to help determine the clinical benefit that would be necessary with TORS to justify its additional cost. TORS would need to add at least 2.4 QALYs when compared with definitive CRT to justify transition over to TORS as a cost-effective advance in treatment. Further analysis of clinical outcomes data will enable a more complete cost-effectiveness analysis. However, given the limited survival of patients with locally advanced tonsillar cancer, the likelihood that TORS will provide a cost-effective clinical benefit may be low. We performed a cost-analysis of the use of TORS for locally advanced tonsillar cancer. Historical data was used to help determine the clinical benefit that would be necessary with TORS to justify its additional cost. TORS would need to add at least 2.4 QALYs when compared with definitive CRT to justify transition over to TORS as a cost-effective advance in treatment. Further analysis of clinical outcomes data will enable a more complete cost-effectiveness analysis. However, given the limited survival of patients with locally advanced tonsillar cancer, the likelihood that TORS will provide a cost-effective clinical benefit may be low.

To determine the significance of histology and treatment modality on overall survival (OS) and cause-specific survival (CSS) in stage IB1 cervical carcinoma. Cases of stage IB1 squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix managed with either radical hysterectomy (RAH), local tumor destruction (including methods such as cryotherapy, laser ablation, excisional biopsy, or trachelectomy, etc.) followed by radiation therapy (RT) which may include external beam radiation therapy (EBRT) and/or brachytherapy (BT), or simple total hysterectomy with RT which may include EBRT and/or BT were abstracted from the SEER database (2004-2008). The primary endpoints of this study were OS and CSS. Statistical methods included Kaplan-Meier and Cox regression analyses. 5-year OS for SCC and AC were 82.9% and 87.2%, respectively (p = 0.06). 5-year CSS for SCC and AC were 92.8% and 90.6%, respectively (p = 0.20). On multivariate Cox regression analysis, patients with AC were not more likely to die of cervical cancer than patients with SC (HR = 1.072, p = 0.821). 5-year OS for patient with IB1 disease was 88.3%, 76.9%, and 84.9% for RAH, local surgery with RT, and TAH with RT, respectively (p = 0.002). 5-year CSS for patients with IB1 disease was 96.6%, 86.1%, and 96.9% for RAH, local surgery with RT, and TAH with RT, respectively (p<0.0001). On multivariate Cox regression analysis, patients who received RAH had improved CSS compared to patients who received local surgery with RT. (HR 4.272, p<0.0001); patients who received RAH did not have improved CSS compared to patients who received TAH with RT (HR 1.007, p = 0.987). No significant difference in OS or CSS between patients with stage IB1 SCC or AC of the cervix was identified. In IB1 patients, management with RAH was associated with improved OS compared to management with local surgery and RT or management with TAH and RT. In IB1 patients, management with RAH or TAH and RT was significantly associated with improved CSS compared to management with local surgery and RT. Radiation is not a preferred method to compensate for inadequate surgery.

Background : To assess feasibility of sparing the neural stem cell compartment (NSC), hippocampus, and limbic circuit during partial brain radiotherapy (PBRT) for pediatric intracranial tumors.Methods : Treatment plans were generated for the following pediatric intracranial tumors: low and high grade gliomas, low grade brainstem glioma, optic nerve glioma, hypothalamic glioma, localized ependymoma, skull base sarcoma, central nervous system (CNS) germinoma (involved field radiotherapy [IFRT] and whole ventricular radiotherapy [WVRT] ), and craniopharyngioma.For each pathology, standard intensity-modulated radiotherapy (IMRT) plans were generated using helical tomotherapy, as well as IMRT plans which spared limbic circuit, hippocampus, and NSC.Biologically equivalent dose for late effects (BED late effects ) was generated for limbic circuit, hippocampus, and NSC.Percent reduction in mean, maximum, and minimum physical dose and BED was calculated between plans. Results :We reduced mean physical dose and BED late effects to these critical structures by 44% and 47.9% respectively (range 5.4-78.8%and 7-80.3%).Greatest benefits in relative dose reduction were seen in high grade hemispheric glioma cases; least relative dose reduction was seen in WVRT cases.Dosimetric coverage of treatment target (PTV) was equivalent in all cases as assessed by D95 and V100 metrics.Integral dose to uninvolved brain was reduced by mean of 7.6% (range -19.3% to +0.3%) in sparing plans.Discussion and Conclusions : It is possible to spare limbic circuit, NSC, and hippocampus during PBRT for primary pediatric intracranial tumors using helical tomotherapy.This approach reduces integral dose delivered to uninvolved normal brain and may reduce late cognitive sequelae of cranial radiotherapy.

The treatment results of patients with locally advanced esophageal carcinomas have evolved since the publication of the first trial of concurrent mitomycin C and 5-fluorouracil with radiotherapy (RT) in 1983. Subsequent studies refined and improved on the concurrent chemotherapy (chemo) with administration of cisplatin and 5-fluorouracil infusion (PF). Chemo (PF) before surgery improved overall survival (OS) in those patients in most of the randomized trials and in meta-analyses. Two courses of PF concurrent with irradiation followed by additional two courses of PF were superior to RT alone without surgery for both groups. Concurrent chemoradiotherapy followed by surgery was found to have statistically improved OS as compared with surgery only in randomized trials and meta-analyses. In most of these studies, it was found that those patients with pathologic complete response to the initial treatment(s) did better than those who had no improvement at all. Current treatment outcome for these diseases is disappointing; newer strategies including induction chemo with the optimal combination, proper dosage of each drug, and proper number of courses before concurrent chemoradiotherapy; improvement in RT; and immunotherapy with or without subsequent surgery are exciting and definitely need to be investigated in prospective randomized trial(s).

To assess frequency of involvement of neural stem cell compartment (NSC) in a series of low grade (World Health Organization [WHO] grades 1/2) and high grade (WHO grades 3/4) gliomas. Initial and subsequent cranial MRI series for 80 low grade gliomas and 104 high grade gliomas treated between 2000 and 2010 at our institution were reviewed. Maximum diameter of gross disease (GTV) was measured, and involvement of NSC was documented if present. For cases not involving NSC, minimum distance from GTV to NSC and distance from NSC to center of tumor were measured. For low grade gliomas which later recurred as high grade gliomas time interval to progression was measured, and each recurrence was evaluated for involvement of NSC. Low grade tumors were stratified by histology (astrocytoma, oligodendroglioma, oligoastrocytoma, or other), tumor grade (1 vs. 2), MIB-1 proliferative status, and pattern of growth (infiltrative vs. localized). High grade tumors were stratified by histology (for grade 3 tumors: astrocytoma, oligodendroglioma, or oligoastrocytoma) and tumor grade (3 vs. 4). All tumors were stratified by maximum diameter of gross disease (≤2 cm vs. >2 cm, ≤3 cm vs. >3 cm). A total of 71.3% (57/80) of low grade tumors involved NSC at presentation. Infiltrative low grade tumors more often involved NSC than localized tumors (94.6% vs. 51.2%, RR 1.85, CI 1.58-2.12, p = 0.13), as did tumors >2 cm or >3 cm vs. smaller tumors (81.8% vs. 21.4% and 86.5% vs. 42.9%, RR 3.82 and 2.02, CI 3.24-4.4 and 1.71-2.33, p = 0.086 and 0.123, respectively). For low grade tumors, tumor grade did not predict NSC involvement (72.4% grade 2 vs. 68.2% grade 1, RR 1.06, CI 1.04-1.08, p = 0.44), nor did histology or MIB-1 proliferative status. Of the 9 high grade recurrences, all were originally grade 2, 77.8% initially involved NSC, and 88.9% of recurrences involved NSC. Ninety-nine percent (103/104) of high grade tumors involved NSC at presentation, 101/104 (97.1%) by GTV, 2/104 pts (1.9%) by edema only. Histology (for grade 3 tumors), tumor grade, and GTV diameter did not affect the rate of NSC involvement. Involvement of NSC by GTV was 90.9% (10/11) for GTV 2cm or less and 95.7% (22/23) for GTV 3cm or less. Infiltrative low grade gliomas frequently involve NSC at presentation and at time of recurrence as high grade glioma, as do de novo high grade gliomas. While tumor volume may affect the rate of NSC involvement by low grade gliomas, it has no influence on the rate of NSC involvement by high grade gliomas, supporting our hypothesis that high grade gliomas and a subset of high risk low grade gliomas arise from the NSC compartment.

Purpose: To assess the feasibility of dosimetrically sparing the hippocampus and neural stem cell (NSC) compartment during whole-brain radiotherapy (WBRT) and prophylactic cranial irradiation (PCI).Methods and Materials: We contoured the brain/brainstem on fused magnetic resonance /computed tomography images as the planning target volume (PTV) in 10 patients, excluding the hippocampus and NSC compartment as organs at risk. PCI and WBRT helical tomotherapy plans were prepared for each patient, with 1.0-cm field width, a pitch of 0.285, and a modulation factor of 2.5. We attempted to maximally spare the hippocampus and NSC compartment while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with a V-100 of >= 95%. Plan quality was assessed by calculating mean dose, equivalent uniform dose (EUD), and biologically equivalent dose (BED) for organs at risk and the percent volume of the PTV receiving the prescribed dose of V-100.Results: In the PCI plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.5 Gy/13.1 Gy/15.7 Gy(2) (BED assuming alpha/beta ratio of 2Gy) and 11.5 Gy/13.1 Gy/12.3 Gy(10) (BED assuming alpha/beta ratio of 10Gy), respectively. In the WBRT plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.8 Gy/14.8 Gy/16.8 Gy(2) and 11.8 Gy/14.8 Gy/12.8 Gy(10), respectively. The mean V-95 for the rest of the brain (PTV) was 96.9% for both the PCI and WBRT plans. Mean PCI and WBRT treatment times were 15.93 min (range, 14.28 min-17.50 min) and 20.18 min (range, 18.43 min-22.32 min), respectively.Conclusions: It is dosimetrically feasible to spare the hippocampus and NSC compartment using helical tomotherapy during the administration of whole-brain irradiation. (C) 2010 Elsevier Inc.

We report the total volume of the limbic circuit in 12 patients and compare the volume of these structures with their reported incidence of involvement by intracranial metastatic disease. This study was performed to assess whether relative limbic circuit sparing by metastatic disease is a purely volumetric phenomenon. We contoured the hippocampus, the rest of the limbic circuit, and the rest of the brain and brainstem (from the foramen magnum cephalad, excluding the CSF spaces and pituitary) on 12 normal cranial MRI studies. We then calculated the volume of each contour, and compared these structures' volumes with their recently reported relative incidence of involvement by intracranial metastatic disease (total limbic circuit 4.9%, hippocampus 0.97%, rest of limbic circuit 3.9%). Total intracranial CNS soft tissue volumes ranged from 1117.6 -1341.3 cm3 (mean 1233.6 cm3). The total limbic circuit constituted 6.4 - 12.1% of this total volume (mean 9.2%), the hippocampus 0.63 - 1.5% (mean 1.0%), and the rest of the limbic circuit 6.0 - 11.1% (mean 8.2%). The recently reported relative proportion of intracranial metastases involving these structures among oligometastatic patients were: total limbic circuit 4.9%, hippocampus 0.97%, and the rest of the limbic circuit 3.9%. The ratios of expected/ identified involvement of these structures by intracranial metastatic disease were: total limbic circuit 1.88, hippocampus 1.0, and the rest of the limbic circuit 2.1. Sparing of the hippocampus by intracranial metastatic disease appears to be a volumetric phenomenon, as evidenced by the 1:1 ratio of (1) the recently reported relative rates of involvement and (2) the relative volume contribution of the hippocampus to the total brain volume as reported in this study. The incidence of involvement of the rest of the limbic circuit by intracranial metastatic disease is lower than would be expected by volume alone if these structures were randomly involved, suggesting that some other mechanism is involved.

To determine the influence of adjuvant therapy on the risk of DID following resection of NSCLC, we compared the actuarial rate of non-cancer related deaths of patients who had been entered in Eastern Cooperative Oncology Group E3590 (a phase III trial of adjuvant therapy in patients with completely resected stages II and IIIA NSCLC) to the actuarial death rate of age and gender matched controls. Following surgery, patients were randomized to receive either PORT (5040 cGy in 28 daily fractions) or CPORT (PORT plus four cycles of cisplatin (60 mg/m2, day 1) and etoposide (120 mg/m2, days 1-3) administered concurrently). The study accrued 488 patients, 242 to the PORT only arm and 246 to the CPORT arm. The overall 4 years actuarial rate of DID for the two arms combined, with a median follow-up of 82 months, was 12.9%, not significantly different from the 10.1% expected rate of DID, based on mortality rates for age and gender matched controls derived from US vital statistics and corrected for smoking status (p=0.16). Survival distributions with regard to DID did not differ between the two treatment arms (p=0.96). DID increased with age (treated as a continuous variable, p<0.01), but was not affected by histology, side of chest irradiated, type of surgery, FEV1 or weight loss in the previous 6 months. The risk of DID following resection of stages II and IIIA NSCLC is not increased in patients who received PORT or CPORT.

Purpose: To analyze the relative contributions of uniformly collected pretreatment patient- and tumor-related variables to survival and to identify the terminal nodes via recursive partitioning analysis (RPA) that could be used as a stratification variable for future Phase III trials.Methods and Materials: From two Intergroup trials (85-01, n = 130; and 94-05, n = 218) and one Radiation Therapy Oncology Group trial (92-07, n = 68), we identified 416 patients who were treated with definitive concomitant cisplatin and 5-FU-based chemoradiotherapy and analyzed their data for survival by RPA to define prognostic classes. The following pretreatment factors were evaluated: histologic type, age, weight loss, Karnofsky performance status, gender, race, T stage, tumor location, tumor size, N stage, and degree of dysphagia. The entire data set was considered as the initial node. The criterion for split points was the smallest p value less than unadjusted 0.05.Results: Of the 416 patients, 336 (81%) were dead at the time of the analysis. The RPA identified only one significant split: pretreatment weight loss in the prior 6 months of <10 % vs. greater than or equal to10 %. After adjusting for multiple comparisons, no other split approached statistical significance.Conclusion: Unlike our experience with malignant glioma, brain metastases, and locally advanced non-small-cell lung cancer, RPA failed to identify novel prognostic information that could be incorporated into the stratification scheme of future chemoradiotherapy trials for esophageal cancer. Furthermore, our analysis validated the percentage of weight loss as a stratification variable for esophageal cancer. (C) 2004 Elsevier Inc.

OBJECTIVES:To test the hypothesis that patients with non-small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non-small cell lung cancer) by site of primary tumor and pattern of lymph node metastases. METHODS:Accurate staging was ensured by mandating either systematic sampling or complete dissection of the ipsilateral mediastinal lymph nodes. The overall survival of patients with left lung non-small cell lung cancer and metastases in only 1 of lymph node levels 5, 6, or 7 and right lung non-small cell lung cancer with metastases in only 1 of levels 4 or 7 was compared with that of patients with N1 disease originating in the same lobe. RESULTS:The median survival of the 172 patients with single-level N2 disease was 35 months (95% confidence interval: 27-40 months) versus 65 months (95% confidence interval: 45-84 months) for the 150 patients with N1 disease (median follow-up 84 months, P =.01). However, among patients with left upper lobe tumors, survival was not significantly different between patients with N1 disease and patients with single-level N2 disease (49 vs 51 months, P =.63). The median survival of the 71 patients with single-level N2 metastases without concomitant N1 disease (skip metastases) was 59 months (95% confidence interval: 36-107 months) versus 26 months (95% confidence interval: 16-36 months) for the 145 patients with both N1 and N2 metastases (P =.001). CONCLUSIONS:Survival of patients with left upper lobe non-small cell lung cancer and metastases to single-level N2 lymph nodes is not significantly different from that of patients with N1 disease. The presence of isolate N2 skip metastases is associated with improved survival when compared with patients with both N1 and N2 disease. Survival should be reported by the lobe of primary tumor and metastatic pattern to guide future clinical trial development, treatment strategies, and revisions of the TNM staging system.