Attention to diet, exercise, and weight in oncology care: Results of an American Society of Clinical Oncology national patient survey.

BACKGROUND: The American Society of Clinical Oncology (ASCO) surveyed cancer patients to assess practice patterns related to weight, diet, and exercise as a part of cancer care. METHODS: An online survey was distributed between March and June 2020 through ASCO channels and patient advocacy organizations. Direct email communication was sent to more than 25,000 contacts, and information about the survey was posted on Cancer.Net. Eligibility criteria included being aged at least 18 years, living in the United States, and having been diagnosed with cancer. Logistic regression was used to determine factors associated with recommendation and referral patterns. RESULTS: In total, 2419 individuals responded to the survey. Most respondents were female (60.1%), 61.1% had an early-stage malignancy, and 48.4% were currently receiving treatment. Breast cancer was the most common cancer (35.7%). The majority of respondents consumed ≤2 servings of fruits and vegetables/d (50.5%) and exercised ≤2 times/wk (50.1%). Exercise was addressed at most or some oncology visits in 56.8% of respondents, diet in 50.1%, and weight in 28.0%. Respondents whose oncology provider provided diet and/or exercise recommendations were more likely to report changes in these behaviors vs. those whose oncology provider did not (exercise: 79.6% vs 69.0%, P < .001; diet 81.1% vs 71.3%, P < .001; weight 81.0% vs 73.3%, P = .003). CONCLUSIONS: In a national survey of oncology patients, slightly more than one-half reported attention to diet and exercise during oncology visits. Provider recommendations for diet, exercise, and weight were associated with positive changes in these behaviors, reinforcing the importance of attention to these topics as a part of oncology care.

A randomized, double-blind, phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive-stage small cell lung cancer: Hoosier Cancer Research Network LUN06-113.

BACKGROUND: This randomized, double-blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive-stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone. METHODS: Patients with previously untreated extensive-stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100 mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run-in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80% power to detect a 3-month difference in the time to progression (TTP) from 4 to 7 months (significance level,.10 [1-sided log-rank test]). RESULTS: Seventy-four patients were enrolled between April 2008 and May 2013. Thirty-three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty-one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo (P = .9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo (P = .4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes. CONCLUSIONS: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive-stage SCLC. Toxicity was increased in comparison with chemotherapy alone. Cancer 2017;123:303-311. © 2016 American Cancer Society.

Successful Therapy with Nivolumab in Metastatic Renal Cell Carcinoma After Multiple Prior Treatments.

Renal cell carcinoma (RCC) is responsible for 80 to 85 percent of all primary renal malignancies. In the United State%, there are about 63,000 new cases and almost :14,000 deaths per year from RCC. Surgical resection of localized RCC can be curative but many patients eventually recur. Immunotherapy appears to be a promising new modality for many malignancies, including RCC. Nivolumab, a specific immunotherapy agent indicated for advanced RCC, may restore antitumor immunity and allow for greater progression-free survival by targeting proteins that negatively regulate T cell immunity. This case study aims to demonstrate the integration of nivolumab into the management of a patient with advanced RCC and provide a stimulus for further investigation and research into this treatment modality.

The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC.

PURPOSE: RTOG 0617 was a phase III randomized trial for patients with unresectable stage IIIA/IIIB non-small cell lung cancer comparing standard-dose (60 Gy) versus high-dose (74 Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617. EXPERIMENTAL DESIGN: From RTOG 0617, 328 of 496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran-Mantel-Haenzel tests and multivariable logistic regression models were used. All statistical tests were two sided, and a P value <0.05 was considered significant. RESULTS: A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients-while the hazard of death was higher in cetuximab-treated patients within year 1 [HR = 3.37, 95% confidence interval (CI): 1.13-10.10, P = 0.030], death was lower from year 1 to 4 (HR = 0.33, 95% CI: 0.11-0.97, P = 0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR = 1.59, 95% CI: 1.11-2.28, P = 0.012). CONCLUSIONS/DISCUSSION: Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy. SIGNIFICANCE: The KRAS-variant is the first functional, inherited miRNA-disrupting variant identified in cancer. Our findings support that cetuximab has a potentially beneficial impact on KRAS-variant patients treated with radiation. The work confirms prior evidence that KRAS-variant patients are a subgroup who are especially sensitive to radiation. These findings further support the potential of this class of variants to enable true treatment personalization, considering the equally important endpoints of response and toxicity.

Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit.

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment. Significance: This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown.

Short Communication: Interim toxicity analysis for patients with limited stage small cell lung cancer (LSCLC) treated on CALGB 30610 (Alliance) / RTOG 0538.

INTRODUCTION: The CALGB 30610/RTOG 0538 randomized trial was designed to test whether high-dose thoracic radiotherapy (TRT) would improve survival compared with 45 Gy twice-daily (BID) TRT in limited stage small cell lung cancer (LSCLC). Two piloted experimental TRT regimens were of interest to study, 70 Gy daily (QD) and 61.2 Gy concomitant boost (CB). Driven by concerns about adequate patient accrual, a study design was employed that eliminated one experimental TRT arm based on early interim toxicity and tolerability, with the study then continuing as a traditional 2-arm phase III study. METHODS: Patients with LSCLC were assigned to receive four cycles of cisplatin and etoposide chemotherapy with one of 3 TRT regimens starting with either the first or second cycle of chemotherapy. The interim endpoint was the cumulative highest toxicity calculated from a scoring system based on treatment-related grade 3 and higher toxicity and the ability to complete therapy in the experimental arms. RESULTS: The final interim analysis was performed after 70 patients accrued to each experimental cohort, and a difference in treatment related toxicity scoring was not found (p = 0.739). Severe esophageal toxicity was comparable in both cohorts. Pulmonary toxicity was low overall, though 4 patients (5.7 %) on the 61.2 Gy arm developed grade 4 dyspnea, which was not observed in the 70 Gy arm. A protocol mandated decision was made to discontinue the 61.2 Gy arm following review of toxicity with the Data and Safety Monitoring Board. CONCLUSION: A randomized trial design using a planned early interim toxicity analysis to discriminate between experimental treatment arms is feasible in a phase III setting. Refinement of the design could increase the likelihood of detecting clinically meaningful differences in toxicity in future studies.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events.

Immune checkpoint inhibitors (ICIs) are the standard of care for the treatment of several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks of toxicity, specifically immune-related adverse events (irAEs). There is a need for clear, effective guidelines for the management of irAEs during ICI treatment, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of single and combination ICI irAEs and ultimately developed evidence- and consensus-based recommendations to assist medical professionals in clinical decision-making and to improve outcomes for patients.

Precision Medicine in Lung Cancer Treatment.

Lung cancer remains second most common cancer in men and women in the United States. More than 50% of patients are diagnosed in the advanced stage. Traditionally, chemotherapy has been the backbone of management of stage IV lung cancer. A better understanding of the molecular pathogenesis has led to rapid development of targeted therapy and immunotherapy. This has led to significant improvement in survival of patients with lung cancer stages III to IV. These drugs are being studied in early stage lung cancer. Several trials are ongoing to improve the survival and quality of life of our patients.

Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer.

PURPOSE: RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non-small-cell lung cancer (NSCLC). METHODS: The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS). RESULTS: Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively (P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months (P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% (P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms. CONCLUSION: A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.

A Case Report of the Clinico-radiologic Challenges of Assessing Treatment Response after Stereotactic Radiation of Oligometastases Preceded by Immunotherapy: Pseudoprogression, Mixed Response Patterns, and Opportunities for Precision Radiation.

As immunotherapy continues to translate to the clinic and is combined with existing modalities, such as radiation therapy, novel treatment response patterns have been observed which complicate conventional clinical assessment and management. Herein, we describe a case study of a patient with non-small cell lung cancer treated initially with definitive chemoradiation who subsequently developed oligorecurrent disease which was managed with nivolumab and then comprehensive salvage stereotactic radiation. Serial radiographic assessment had shown worsening at these limited sites of disease after initiating immunotherapy, improvement after radiation, and then heterogeneous response behavior across sites during longer-term follow-up. Given the dual effects ablative radiation may have in the context of global immune checkpoint inhibition, both cytotoxic and synergistic immune-related, assessment of treatment response to such treatment is complicated. Such assessment is further complicated by novel immunotherapy response phenomena, e.g. pseudoprogression, which are being uncovered and are not fully characterized. Current clinical and radiologic assessment strategies are inadequate to interrogate and discern between immunomodulation-influenced response behavior and further diagnostic innovation is warranted to meet the needs of evolving clinical practice in the era of immunotherapy.

Relationship between symptom change, objective tumor measurements, and performance status during chemotherapy for advanced lung cancer.

PURPOSE: Our objective was to identify which symptoms of advanced lung cancer are most likely to change with objective tumor measurements (progressions and responses) or changes in performance status (PS). PATIENTS AND METHODS: Eighty patients with advanced non-small-cell lung cancer were studied during the first 12 weeks of chemotherapy. Symptoms were assessed weekly through telephone administration of the Functional Assessment of Cancer Therapy-Lung Symptom Index-12. Data on PS were collected from patients every 3 weeks. Symptom reports were mapped onto clinical events (progression or response as determined by clinicians) and PS assessments. RESULTS: Disease progression and declining PS were associated with worsening of several symptoms. Pain, shortness of breath, cough, weight loss, and appetite loss worsened most from before to after progression. Patients with an objective response to chemotherapy reported more fatigue and difficulty breathing at response than before response. However, unlike patients who experienced progression, patients responding to chemotherapy never or rarely complained of clinically significant pain, weight loss, cough, chest tightness, nausea, or confusion before, during, or after response. With the exception of bother with side effects of treatment, confusion, and difficulty breathing, symptoms tracked fairly closely over the 12 weeks with changes in PS. Declining PS was associated with considerably more symptom worsening than unchanged or improved PS, independent of treatment response. CONCLUSION: These data can help the clinician identify symptoms of lung cancer most reliably associated with objective responses and perceived changes in functional status during chemotherapy. Symptom self-reports could be used by clinicians to monitor patient status and possibly inform treatment modification.

Phase II study of carboplatin, pemetrexed, and bevacizumab in advanced nonsquamous non-small-cell lung cancer.

Lung cancer remains the leading cause of cancer death throughout the world. Despite new chemotherapeutic, immunomodulating and molecularly targeted agents, patients with locally advanced or metastatic disease still have a poor prognosis. This trial looked to combine antiangiogenic therapy with a first-line cytotoxic chemotherapy doublet, hoping to extend median progression-free survival (PFS) while minimizing toxicity in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). In this single institution, single-arm study, 51 patients (age >18 yo) were followed from 2007 to 2012. Patients with stage IV nonsquamous NSCLC and patients with recurrent unresectable disease (nonradiation candidates) were eligible. Treatment consisted of carboplatin AUC 5 IV 30-60 minutes, pemetrexed 500/mg2 IV 10 minutes, bevacizumab 15 mg/kg IV (90 minutes 1st dose, 60 minutes 2nd dose, 30 minutes subsequent doses). Treatment was administered every 21 days and planned for 6 cycles, in the absence of disease progression or unacceptable toxicities. Growth factor support was not permitted prophylactically but allowed for toxicities, as were dose reductions. Maintenance treatment for those with stable disease or better consisted of Bevacizumab 15 mg/kg every 3 weeks for up to 1 year. Between November 2007 and March 2012, 51 patients were followed in the phase II trial of carboplatin, pemetrexed, and bevacizumab. Patients were enrolled over a 24-month period. After the end of treatment visits, subjects were followed at least every 3 months for survival data. The median follow-up period was 49 weeks (6 weeks to 178), and the median number of treatment cycles was 6 (range, 1-6). Among the 50 patients assessable for response, median overall survival was 49 weeks (95% CI, 0-62.7) with median PFS of 28 weeks (95% CI, 0-132.4). A complete or partial response was seen in 28 (59.5%) patients. Grade 3-4 treatment-related adverse events occurred in 9 (17.6%) of 51 patients; the most common were thrombocytopenia (4 [7.8%]) and neutropenia (3 [5.9%]). Three (5.8%) of 51 patients were discontinued because of treatment-related adverse events (grade 3 diarrhea, thrombocytopenia, dehydration, fatigue, and grade 4 respiratory distress), and 1 patient (1.9%) was found to be ineligible due to anticoagulation use. A novel 3-drug combination for advanced nonsquamous NSCLC shows promising efficacy with modest toxicity.

Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies: HOG LUN 07-130.

OBJECTIVES: Relapsed small cell lung cancer (SCLC) has limited treatment options. Anthracyclines and cyclophosphamide have shown synergy in many tumors. Amrubicin (AMR) and cyclophosphamide both have single-agent activity in SCLC. This phase I trial evaluated the combination of AMR and cyclophosphamide in refractory solid organ malignancies and in relapsed SCLC. MATERIALS AND METHODS: The primary endpoint was to determine maximum-tolerated dose and dose-limiting toxicities of the combination. Eligible patients were enrolled in sequential dose escalation cohorts in a standard 3+3 design. Treatment consisted of cyclophosphamide IV at 500 mg/m on day 1 with escalating doses of AMR IV on days 1 to 3 (25 to 40 mg/m with increments of 5 mg/m per cohort). Cycles were repeated every 21 days. Exploratory objectives analyzed the presence of NQO1 polymorphisms and topoisomerase IIA amplification and correlation with response. RESULTS: Thirty-six patients were enrolled, of whom 18 patients had SCLC (50%). Maximum-tolerated dose was determined to be dose level 2 (cyclophosphamide 500 mg/m, AMR 30 mg/m) due to grade 4 thrombocytopenia. The main grade 3 to 4 toxicities were hematologic. Efficacy results are available for 34 patients. Partial responses, stable disease, and progressive disease rates in the overall study population were 20.6% (n=7), 38.2% (n=13), and 41.2% (n=14), respectively. Partial response, stable disease, and progressive disease rates in the SCLC patients and 1 patient with extrathoracic small cell were 36.8% (n=7), 26.3% (n=5), and 36.8% (n=7), respectively. There was no correlation between topoisomerase IIA amplification or NQO1 polymorphisms and response. CONCLUSIONS: AMR and cyclophosphamide can be safely combined with little activity observed in heavily pretreated SCLC patients.

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan.

Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR.

Safety and Immunogenicity of the PRAME Cancer Immunotherapeutic in Patients with Resected Non-Small Cell Lung Cancer: A Phase I Dose Escalation Study.

INTRODUCTION: Adjuvant platinum-based chemotherapy is standard treatment for surgically resected stage II to IIIA NSCLC, but the relapse rate is high. The preferentially expressed antigen of melanoma (PRAME) tumor antigen is expressed in two-thirds of NSCLC and offers an attractive target for antigen-specific immunization. A phase I dose escalation study assessed the safety and immunogenicity of a PRAME immunotherapeutic consisting of recombinant PRAME plus proprietary immunostimulant AS15 in patients with surgically resected NSCLC (NCT01159964). METHODS: Patients with PRAME-positive resected stage IB to IIIA NSCLC were enrolled in three consecutive cohorts to receive up to 13 injections of PRAME immunotherapeutic (recombinant PRAME protein dose of 20 µg, 100 µg, or 500 µg, with a fixed dose of AS15). Adverse events, predefined dose-limiting toxicity, and the anti-PRAME humoral response (measured by enzyme-linked immunosorbent assay) were coprimary end points. Anti-PRAME cellular responses were assessed. RESULTS: A total of 60 patients were treated (18 received 20 µg of PRAME, 18 received 100 µg of PRAME, and 24 received 500 µg of PRAME). No dose-limiting toxicity was reported. Adverse events considered by the investigator to be causally related to treatment were grade 1 or 2, and most were injection site reactions or fever. All patients had detectable anti-PRAME antibodies after four immunizations. The percentages of patients with PRAME-specific CD4-positive T cells were higher at the dose of 500 µg compared with lower doses. No predefined CD8-positive T-cell responses were detected. CONCLUSION: The PRAME immunotherapeutic had an acceptable safety profile. All patients had anti-PRAME humoral responses that were not dose related, and 80% of those treated at the highest dose showed a cellular immune response. The dose of 500 µg was selected. However, further development was stopped after negative results with a similar immunotherapeutic in patients with NSCLC.

Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597.

PURPOSE: Gemcitabine has shown a broad range of activity in solid tumors, including previously untreated small-cell lung cancer (SCLC). The objective of this phase II trial was to investigate the activity of gemcitabine in patients with relapsed SCLC. PATIENTS AND METHODS: SCLC patients with measurable disease who had experienced treatment failure with one prior chemotherapy regimen were considered eligible. Patients were required to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and adequate organ function; signed informed consent was also required. Treatment consisted of gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Patients were stratified according to their previous response to first-line chemotherapy (primary refractory v primary sensitive disease). RESULTS: Forty-six patients were enrolled onto this phase II trial (20 refractory and 26 sensitive patients). Forty-two of these patients were assessable for response and survival, and 44 were assessable for toxicity. Median patient age was 60 years, and median ECOG performance status was 1. Principal grade 3/4 hematologic toxicities included neutropenia (27%) and thrombocytopenia (27%). The main grade 3/4 nonhematologic toxicities were pulmonary (9%) and neurologic toxicity (14%). Objective responses occurred in 11.9% of patients overall, including one patient with refractory SCLC (5.6%) and four patients with sensitive SCLC (16.7%). Median survival for the overall group was 7.1 months. Survival was not significantly different for patients with refractory versus sensitive disease. CONCLUSION: Gemcitabine has modest activity in previously treated SCLC patients. The favorable toxicity profile warrants further investigation, either in combination chemotherapy regimens or with targeted biologic compounds.

Intraoperative sentinel lymph node mapping in non-small-cell lung cancer improves detection of micrometastases.

PURPOSE: Lymph node metastases are the most significant prognostic factor in localized non-small-cell lung cancer (NSCLC). Nodal micrometastases may not be detected with current standard histologic methods. We performed intraoperative technetium-99m ((99m)Tc) sentinel lymph node (SN) mapping in patients with resectable NSCLC. This study aimed to identify the first station of nodal drainage of operable lung cancers. Serial section histology and immunohistochemistry were used to validate the SN and to identify the presence of micrometastatic disease. PATIENTS AND METHODS: One hundred patients with potentially resectable suspected NSCLC were enrolled. At thoracotomy, the primary tumor was injected with 0.25 to 2 mCi (99m)Tc. Intraoperative scintigraphic readings of both the primary tumor and lymph nodes were obtained with a hand-held gamma counter. Anatomic resection with a mediastinal node dissection was then performed. RESULTS: Nine of the 100 patients did not have NSCLC (seven benign lesions and two metastatic tumors) and were excluded. Seventy-eight (86%) of 91 patients had a SN identified and a complete resection. Sixty-nine (88.5%) out of the 78 SNs were classified as true-positive with no metastases found in other intrathoracic lymph nodes without concurrent SN involvement. In nine patients, the SN was the only positive node. In seven of these nine patients, the SN was found to harbor only micrometastatic disease. CONCLUSION: Intraoperative SN mapping with (99m)Tc is an accurate way to identify the first site of lymphatic tumor drainage in NSCLC. This method may also improve the precision of pathologic staging.

Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: results from two consecutive phase I/II trials.

PURPOSE: The management of unresectable locally advanced breast cancer (ULABC) remains a major challenge because of the necessity both to treat local disease and to prevent distant disease. Two consecutive Phase I/II trials of concomitant chemotherapy and radiation (CRT) were performed to attempt to address both local and distant disease control in ULABC. This analysis focuses on rates of locoregional control and radiation-associated acute and late complications. METHODS AND MATERIALS: Thirty-three patients with unresectable locally advanced or inflammatory breast cancers (T4N0-3M0-1) or locally recurrent disease were treated with CRT on two consecutive Phase I/II trials. Radiotherapy consisted of 60-70 Gy to the breast or chest wall and 60 Gy to draining lymphatics in a week-on/week-off (WO/WO) schedule. Chemotherapy consisted of either continuous infusion or bolus paclitaxel +/- vinorelbine. A subset analysis of 16 patients with nonmetastatic ULABC Stage IIIB-C (T4N0-3M0) was performed. Among this cohort, 13 patients (81%) underwent planned mastectomy after CRT. RESULTS: Of the 16 patients with Stage IIIB-C disease, acute toxicity included moist desquamation (n = 8) and Grade 3-4 neutropenia (n = 3). Late toxicity included breast reconstruction loss, decreased range of arm motion, lymphedema, and skin toxicity, although none was life-threatening. Of 15 assessable patients, 14 had a clinical response, 7 had a pathologic complete response (pCR) including 6 of 13 patients undergoing mastectomy. With a median follow-up for living patients of 43.8 months, the 4-year actuarial locoregional control, disease-free survival, and overall survival were 83%, 33%, and 56% respectively. CONCLUSIONS: Concurrent WO/WO radiation therapy and paclitaxel +/- vinorelbine is effective locoregional therapy for ULABC with an acceptable toxicity profile. Further investigation of concurrent chemoradiotherapy in ULABC is warranted.

Quality of life in lung cancer: the validity and cross-cultural applicability of the Functional Assessment Of Cancer Therapy-Lung scale.

This article discusses quality of life in lung cancer: the validity and cross-cultural applicability of the Functional Assessment of Cancer Therapy-Lung scale.

Primary osteosarcoma of the breast.

Primary osteosarcoma of the breast is a rare malignant tumor. We report on an 80-year-old woman who presented with a right breast lump and a mammogram suggestive of carcinoma. The lesion was excised and histological features of the tumor were consistent with primary osteosarcoma. Due to insufficient resection margins, segmental mastectomy was performed to establish clear margins and failed to show any remaining tumor. There was no evidence of a separate primary tumor, and a metastatic work-up was unrevealing. We determined that primary treatment with segmental mastectomy was adequate and no further treatment was necessary. She remains disease free at 15 months.