Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. METHODS: Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. RESULTS: Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p = .0008) and FACT-L scores (DID, 2.47; p = .004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p = .06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. CONCLUSIONS: SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

Adverse Events Following Limited Resection versus Stereotactic Body Radiation Therapy for Early Stage Lung Cancer.

Rationale: Approximately a quarter of patients with early stage lung cancer are not medically fit for lobectomy. Limited resection and stereotactic body radiation therapy (SBRT) have emerged as alternatives for these patients. Given the equipoise on the effectiveness of the two treatments, treatment-related adverse events (AEs) could have a significant impact on patients' decision-making and treatment outcomes. Objectives: To compare the AE profile between SBRT versus limited resection. Methods: Data were derived from a prospective cohort of patients with stage I-IIA non-small cell lung cancer who were deemed as high-risk for lobectomy recruited from five centers across the United States. Propensity scores and inverse probability weighting were used to compare the rates of 30- and 90-day AEs among patients treated with limited resection versus SBRT. Results: Overall, 65% of 252 patients underwent SBRT. After adjusting for propensity scores, there was no significant difference in developing at least one AE comparing SBRT to limited resection (odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.65-1.55 and OR: 1.27; 95% CI: 0.84-1.91 at 30 and 90 days, respectively). SBRT was associated with lower risk of infectious AEs than limited resection at 30 days (OR: 0.05; 95% CI: 0.01-0.39) and 90 days posttreatment (OR: 0.41; 95% CI: 0.17-0.98). Additionally, SBRT was associated with persistently elevated risk of fatigue (OR: 2.47; 95% CI: 1.34-4.54 at 30 days and OR: 2.69; 95% CI: 1.52-4.77 at 90 days, respectively), but significantly lower risks of respiratory AEs (OR: 0.36; 95% CI: 0.20-0.65 and OR: 0.51; 95% CI: 0.31-0.86 at 30 and 90 days, respectively). Conclusions: Though equivalent in developing at least one AE, we found that SBRT is associated with less toxicity than limited resection in terms of infectious and respiratory AEs but higher rates of fatigue that persisted up to 3 months posttreatment. This information, combined with data about oncologic effectiveness, can help patients' decision-making regarding these alternative therapies.

Forest bat population dynamics over 14 years at a climate refuge: Effects of timber harvesting and weather extremes.

Long-term data are needed to explore the interaction of weather extremes with habitat alteration; in particular, can 'refugia' buffer population dynamics against climate change and are they robust to disturbances such as timber harvesting. Because forest bats are good indicators of ecosystem health, we used 14 years (1999-2012) of mark-recapture data from a suite of small tree-hollow roosting bats to estimate survival, abundance and body condition in harvested and unharvested forest and over extreme El Niño and La Niña weather events in southeastern Australia. Trapping was replicated within an experimental forest, located in a climate refuge, with different timber harvesting treatments. We trapped foraging bats and banded 3043 with a 32% retrap rate. Mark-recapture analyses allowed for dependence of survival on time, species, sex, logging treatment and for transients. A large portion of the population remained resident, with a maximum time to recapture of nine years. The effect of logging history (unlogged vs 16-30 years post-logging regrowth) on apparent survival was minor and species specific, with no detectable effect for two species, a positive effect for one and negative for the other. There was no effect of logging history on abundance or body condition for any of these species. Apparent survival of residents was not strongly influenced by weather variation (except for the smallest species), unlike previous studies outside of refugia. Despite annual variation in abundance and body condition across the 14 years of the study, no relationship with extreme weather was evident. The location of our study area in a climate refuge potentially buffered bat population dynamics from extreme weather. These results support the value of climate refugia in mitigating climate change impacts, though the lack of an external control highlights the need for further studies on the functioning of climate refugia. Relatively stable population dynamics were not compromised by timber harvesting, suggesting ecologically sustainable harvesting may be compatible with climate refugia.

Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control.

BACKGROUND: Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies. METHODS: The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) treated with SBRT were reviewed. Local control (LC) was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV) on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED) to characterize the dose-control relationship using a logistic tumor control probability (TCP) model. Additionally, the kinetics of decline in maximum SUV (SUVmax) were analyzed. RESULTS: The SBRT regimen was 40-50 Gy/5 fractions (n = 23) or 42-60 Gy/3 fractions (n = 30) delivered to lung (n = 39), liver (n = 11) and bone (n = 3) metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68). The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05). The actuarial rate of LC at 24 months was 100% for SFED ≥45 Gy v 54% for SFED <45 Gy. TCP modeling indicated that to achieve ≥90% 2 yr LC in a 3 fraction regimen, a prescription dose of at least 48 Gy is required. In 9 patients followed with PET scans, the mean pre-SBRT SUVmax was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3. CONCLUSIONS: An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.

Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases.

PURPOSE: To evaluate the efficacy and tolerability of high-dose stereotactic body radiation therapy (SBRT) for the treatment of patients with one to three lung metastases. PATIENTS AND METHODS: Patients with one to three lung metastases with cumulative maximum tumor diameter smaller than 7 cm were enrolled and treated on a multi-institutional phase I/II clinical trial in which they received SBRT delivered in 3 fractions. In phase I, the total dose was safely escalated from 48 to 60 Gy. The phase II dose was 60 Gy. The primary end point was local control. Lesions with at least 6 months of radiographic follow-up were considered assessable for local control. Secondary end points included toxicity and survival. RESULTS: Thirty-eight patients with 63 lesions were enrolled and treated at three participating institutions. Seventy-one percent had received at least one prior systemic regimen for metastatic disease and 34% had received at least two prior regimens (range, zero to five). Two patients had local recurrence after prior surgical resection. There was no grade 4 toxicity. The incidence of any grade 3 toxicity was 8% (three of 38). Symptomatic pneumonitis occurred in one patient (2.6%). Fifty lesions were assessable for local control. Median follow-up for assessable lesions was 15.4 months (range, 6 to 48 months). The median gross tumor volume was 4.2 mL (range, 0.2 to 52.3 mL). Actuarial local control at one and two years after SBRT was 100% and 96%, respectively. Local progression occurred in one patient, 13 months after SBRT. Median survival was 19 months. CONCLUSION: This multi-institutional phase I/II trial demonstrates that high-dose SBRT is safe and effective for the treatment of patients with one to three lung metastases.

Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases.

PURPOSE: To evaluate the efficacy and tolerability of high-dose stereotactic body radiation therapy (SBRT) for the treatment of patients with one to three hepatic metastases. PATIENTS AND METHODS: Patients with one to three hepatic lesions and maximum individual tumor diameters less than 6 cm were enrolled and treated on a multi-institutional, phase I/II clinical trial in which they received SBRT delivered in three fractions. During phase I, the total dose was safely escalated from 36 Gy to 60 Gy. The phase II dose was 60 Gy. The primary end point was local control. Lesions with at least 6 months of radiographic follow-up were considered assessable for local control. Secondary end points were toxicity and survival. RESULTS: Forty-seven patients with 63 lesions were treated with SBRT. Among them, 69% had received at least one prior systemic therapy regimen for metastatic disease (range, 0 to 5 regimens), and 45% had extrahepatic disease at study entry. Only one patient experienced grade 3 or higher toxicity (2%). Forty-nine discrete lesions were assessable for local control. Median follow-up for assessable lesions was 16 months (range, 6 to 54 months). The median maximal tumor diameter was 2.7 cm (range, 0.4 to 5.8 cm). Local progression occurred in only three lesions at a median of 7.5 months (range, 7 to 13 months) after SBRT. Actuarial in-field local control rates at one and two years after SBRT were 95% and 92%, respectively. Among lesions with maximal diameter of 3 cm or less, 2-year local control was 100%. Median survival was 20.5 months. CONCLUSION: This multi-institutional, phase I/II trial demonstrates that high-dose liver SBRT is safe and effective for the treatment of patients with one to three hepatic metastases.

Benefit of postoperative adjuvant chemoradiotherapy in locoregionally advanced esophageal carcinoma.

OBJECTIVE: We sought to determine whether chemoradiotherapy after esophagectomy improves survival. METHODS: From 1994 to 2000, 31 patients with locoregionally advanced esophageal carcinoma (90% pT3, 81% pN1, and 13% pM1a) received postoperative adjuvant chemoradiotherapy. Concurrently, 52 patients with advanced carcinoma underwent esophagectomy alone and survived at least 10 weeks, the time frame for adjuvant therapy. A propensity score based on demographic, tumor, and surgical factors was used to identify matched pairs to determine the association of adjuvant therapy with outcomes. RESULTS: For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year survivals were 28 versus 14 months, 68% +/- 8.4% versus 60% +/- 6.8%, and 44% +/- 9.0% versus 17% +/- 5.6%, respectively (P =.05). Similarly, risk-unadjusted median time to recurrence was 25 versus 13 months (P =.15), and median recurrence-free survival was 22 versus 11 months (P =.04). Among propensity-matched patients, median, 1-year, and 4-year survivals for those receiving adjuvant therapy versus esophagectomy were 28 versus 15 months, 60% +/- 11.0% versus 65% +/- 10.7%, and 44% +/- 11.3% versus 0% (P =.05). Median time to recurrence was 25 versus 13 months (P =.04), and recurrence-free survival was 22 versus 10 months (P =.02). CONCLUSION: In patients with locoregionally advanced esophageal carcinoma, addition of postoperative adjuvant chemoradiotherapy to esophagectomy alone doubled survival time, time to recurrence, and recurrence-free survival. Patients with locoregionally advanced carcinoma after esophagectomy should be considered for adjuvant therapy.

Value of accelerated multimodality therapy in stage IIIA and IIIB non-small cell lung cancer.

OBJECTIVES: This study was undertaken to assess accelerated multimodality therapy in patients with IIIA and IIIB non-small cell lung cancer in terms of toxicity, feasibility, response, survival, and recurrence (value) and to identify predictors of pathologic response and improved survival. METHODS: Between October 1994 and September 2000, a total of 105 patients with stage pIIIA (n = 78) or pIIIB (n = 27) non-small cell lung cancer were enrolled in a study of accelerated multimodality therapy, consisting of hyperfractionated radiotherapy with concurrent chemotherapy (paclitaxel and cisplatin) followed by resection and postoperative chemoradiation. Multivariable correlates of pathologic response and survival were assessed. RESULTS: Toxic effects related to induction therapy necessitated hospitalization in 40% of patients (n = 42); treatment-related mortality was 9% (n = 9). With respect to feasibility, 100% of patients completed induction therapy, 93% (n = 98) of cancers were operable, 79% (n = 83) of cancers were curatively resectable, and 77% (n = 81) of patients completed all therapy. Sterilization of mediastinal nodes was similar (P =.6) for pN2 (35%) and pN3 (30%) disease. Median, 2-year, and 5-year survivals were 27 months, 53%, and 32%, respectively. Locoregional recurrence, distant recurrence, and both were seen in 6% (n = 6), 45% (n = 47), and 3% (n = 3) of patients, respectively. Pathologic response was not predictable. Nodal status predicted incrementally decreasing survival for patients with cancers downstaged to ypN0 or ypN1 (n = 35) versus ypN2 (n = 44) versus ypN3 (n = 20; P <.001). In addition, advancing age, squamous histologic type, and higher pT predicted poorer survival. CONCLUSIONS: Accelerated multimodality therapy is equally valuable in IIIA and IIIB non-small cell lung cancers. Despite unpredictable response to induction therapy, younger patients and those with nonsquamous histologic type, sterilization of mediastinal lymph nodes, and lower pT benefit most. A ypN2 stage reduces but does not preclude long-term survival.

Factors associated with improved survival in patients with brain metastases from esophageal cancer: a retrospective review.

There are over 200,000 cases of brain metastases (BrM) every year, but very few are from esophageal cancer primaries. In order to determine predictors for outcome of these patients, the authors conducted a retrospective review of twenty-seven patients with BrM from esophageal carcinoma diagnosed at the Cleveland Clinic Foundation between 1991 and 2001. For the entire cohort, median follow-up and median survival was 3.6 months and 3.6 months, respectively. On univariate analysis, patients with Karnofsky Performance Status (KPS) >/= 70, low recursive partitioning analysis score, single BrM, no systemic disease, and aggressive treatment [surgery, stereotactic radiosurgery (SRS) + whole brain radiation (WBRT), SRS + surgery + WBRT, surgery + WBRT)] had a significantly improved survival. In a multivariate model, patients with higher KPS and aggressive treatment had improved survival. The 1-year survival for the WBRT alone group and the aggressive treatment group was 6%, and 36% respectively. We conclude that based on the data presented here, patients with BrM from esophageal cancer have poor outcome. Aggressive treatment and favorable KPS are associated with longer survival for selected patients. We recommend esophageal cancer patients with BrM be enrolled in clinical trials to better delineate the role of treatment and potentially improve results.

Effect of anatomic, procedural, and dosimetric variables on urinary retention after permanent iodine-125 prostate brachytherapy.

OBJECTIVES: To correlate anatomic, procedural, and dosimetric parameters with the rate of intermittent self-catheterization (ISC). METHODS: The records of 402 patients with a median age of 69 years treated with 125I prostate seed implantation from 1996 to 2001 were reviewed for the use of ISC. The records were examined for the preimplant factors: prostate volume, use of androgen deprivation, and prostate length. The intraprocedural factor reviewed was the number of needles used. The following postimplant information was also collected: preimplant transrectal ultrasound-generated prostate volume/postimplant computed tomography-generated prostate volume ratio, V100, V150, V200, V300, V400, D90, and D100. Correlation was assessed using logistic regression analysis. RESULTS: Forty-four patients had to use ISC (10.9%). The mean and median duration of ISC was 11.9 and 6 weeks, respectively. From univariate analysis, prostate length and prostate volume were found to be statistically significant predictors of ISC after 125I prostate seed implantation with a P value of 0.0002 and 0.0042, respectively. With multivariate analysis, only prostate length was a statistically significant predictor of ISC use after 125I prostate seed implantation (P = 0.0095). CONCLUSIONS: Prostate length is an important predictor of ISC after 125I prostate seed implantation.

Stage III non-small cell lung cancer and metachronous brain metastases.

OBJECTIVES: This study was undertaken to identify management strategies that maximize survival of patients with stage III non-small cell lung cancer and metachronous brain metastases and to determine whether any apparent improved survival was due to treatment or simply to patient selection. METHODS: Treatment evaluations of both primary non-small cell lung cancer and brain metastases were performed in 91 patients. Optimal treatment was identified by multivariable analysis. Propensity scoring and multivariable analysis were used to separate treatment benefit from patient selection. RESULTS: Risk-unadjusted median, 12-, and 24-month survivals were 5.2 months, 22%, and 10%, respectively. Younger age (P =.006), good performance status (P =.003), stage IIIA (P =.001), lung resection (P =.02), no other systemic metastases at time of diagnosis of brain metastases (P =.02), and either metastasectomy (P <.001) or stereotactic radiosurgery (P <.001) predicted best survival. However, metastasectomy or stereotactic radiosurgery was more common after lung resection (P =.02) and in patients with good performance status (P =.006), no other systemic metastases at time of diagnosis of brain metastases (P =.01), and fewer brain metastases (P <.001), suggesting that the patients with the best risk profile were selected for aggressive therapy of both lung primary and brain metastases. Despite this selection, analysis of propensity-matched patients demonstrated the benefit of lung resection and metastasectomy or stereotactic radiosurgery (P <.001). CONCLUSIONS: Younger patients with resected stage IIIA non-small cell lung cancer who have isolated metachronous brain metastases and good performance status do best when treated with metastasectomy or stereotactic radiosurgery. This survival benefit is a brain treatment effect, not the result of selecting the best patients for aggressive therapy.

Survival by radiation therapy oncology group recursive partitioning analysis class and treatment modality in patients with brain metastases from malignant melanoma: a retrospective study.

BACKGROUND: In a population of patients with brain metastases from melanoma, the authors sought to determine whether various therapies provided any benefit at all, whether local therapy was better than whole brain radiotherapy (WBRT), and whether combined local therapy and WBRT provided any advantage over local therapy alone. They also analyzed survival according to a Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) to determine how well the RTOG RPA classes predicted survival in this patient population and whether treatments varied in effectiveness from category to category. METHODS: A total of 74 patients with brain metastases from melanoma were treated at The Cleveland Clinic Foundation between 1984 and 1998. For this study, the authors reviewed patient charts and confirmed survival status. Survival was compared by treatment modality (surgical resection, WBRT, stereotactic radiosurgery, or WBRT combined with local therapy). Survival also was compared according to the RTOG RPA prognostic classes (Class 1, Class 2, or Class 3), which has not been validated previously in patients with malignant melanoma. RESULTS: The median survival was 5.5 months for all patients. Survival varied significantly by RTOG prognostic class; The median survival was 10.5 months (range, 2.2-99.2 months) for patients in Class 1, 5.9 months (range, 0.2-43.9 months) for patients in Class 2, and 1.8 months (range, 0.1-6.9 months) for patients in Class 3 (P < 0.0001). Survival analysis showed that combined treatment offered significantly better survival (P < 0.0001; combined vs. other). The median survival was 8.8 months (range, 1.8-99.2 months) for the combined therapy group, 4.8 months (range, 1.2-27.8 months) for the local therapy alone group, 2.3 months (range, 0.2-9.6 months) for the WBRT alone group, and 1.1 months (0.1-3.0 months) for the group that received no therapy. CONCLUSIONS: Adding WBRT to local therapy may improve survival in this group of patients: Combined therapy was superior to WBRT alone. The RPA classification scheme likely has prognostic value for patients with brain metastases from malignant melanoma. Prospective studies are required to overcome selection bias and confirm these results.