Lynn D. Wilson

Postoperative Radiotherapy for Stage II or III Non–Small-Cell Lung Cancer Using the Surveillance, Epidemiology, and End Results Database

PURPOSE To investigate the association between survival and postoperative radiotherapy (PORT) in patients with resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Within the Surveillance, Epidemiology, and End Results database, we selected patients with stage II or III NSCLC who underwent a lobectomy or pneumonectomy. Only those patients coded as receiving PORT or observation were included. To account for perioperative mortality, we excluded patients who survived less than 4 months. As a result of our inclusion criteria, we selected a total of 7,465 patients, with a median follow-up time of 3.5 years for patients still alive. RESULTS Predictors for the use of PORT included age less than 50 years, higher American Joint Committee on Cancer stage, T3-4 tumor stage, larger tumor size, advanced node stage, greater number of lymph nodes involved, and a ratio of lymph nodes involved to lymph nodes sampled approaching 1.00. On multivariate analysis, older age, T3-4 tumor stage, N2 node stage, male sex, fewer sampled lymph nodes, and greater number of involved lymph nodes had a negative impact on survival. The use of PORT did not have a significant impact on survival. However, in subset analysis for patients with N2 nodal disease (hazard ratio [HR] = 0.855; 95% CI, 0.762 to 0.959; P = .0077), PORT was associated with a significant increase in survival. For patients with N0 (HR = 1.176; 95% CI, 1.005 to 1.376; P = .0435) and N1 (HR = 1.097; 95% CI, 1.015 to 1.186; P = .0196) nodal disease, PORT was associated with a significant decrease in survival. CONCLUSION In a population-based cohort, PORT use is associated with an increase in survival in patients with N2 nodal disease but not in patients with N1 and N0 nodal disease.

A retrospective review of 1349 cases of sebaceous carcinoma.

Sebaceous carcinoma is a rare and aggressive cutaneous carcinoma. It is believed that this malignancy predominates in the periocular region and occurs more frequently in Asian populations and in women. The objective of the current study was to analyze demographic characteristics and outcomes for patients with this malignancy from a large United States‐based population registry.

Sézary syndrome: Immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC)

Sézary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine. Finally, guidelines for the treatment of SS and suggestions for adjuvant treatment are noted.

The Future of Radiation Oncology in the United States From 2010 to 2020: Will Supply Keep Pace With Demand?

PURPOSE Prior studies forecasted an incipient shortage of medical oncologists as a result of the aging US population, but the radiation oncology workforce has not been studied. Accordingly, we projected demand for radiation therapy and supply of radiation oncologists in 2010 and 2020 to determine whether a similar shortage may exist for this specialty. METHODS Demand for radiation therapy in 2010 and 2020 was estimated by multiplying current radiation utilization rates (as calculated with Surveillance, Epidemiology, and End Results data) by population projections from the Census Bureau. Supply of radiation oncologists was projected using data from the American Board of Radiology inclusive of current radiation oncologists and active residents, accounting for variation in full-time equivalent status and expected survival by age and sex. RESULTS Between 2010 and 2020, the total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 22%, from 470,000 per year to 575,000 per year. In contrast, assuming that the current graduation rate of 140 residents per year remains constant, the number of full-time equivalent radiation oncologists is expected to increase by only 2%, from 3,943 to 4,022. The size of residency training classes for the years 2014 to 2019 would have to double to 280 residents per year in order for growth in supply of radiation oncologists to equal expected growth in demand. CONCLUSION Demand for radiation therapy is expected to grow 10 times faster than supply between 2010 and 2020. Research is needed to explore strategies to enhance capacity to deliver quality radiation therapy despite increased patient loads.

Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides)

PURPOSE Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for T1/T2 CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. METHODS AND MATERIALS Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m2, 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received topical nitrogen mustard, 22% received a combination of therapies exclusive of PUVA, and 9% received no adjuvant therapy. Patients were balanced in all subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range 20-88), with a median follow-up time of 62 months (range 3-179). RESULTS Within 1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved a complete remission. Stratified by adjuvant therapy, none of six T1 and one of eight T2 patients who received adjuvant PUVA failed within the first 3 years after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving other or no adjuvant treatment failed within the same time course. The 5-year OS for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100% versus a 5-year OS for the non-PUVA group of 82% (p < 0.10). The 5-year DFS for the entire cohort was 53%. Those who received PUVA had a 5-year DFS of 85% versus a 5-year DFS for the non-PUVA group of 50% (p < 0.02). By T stage, those with T1 receiving PUVA exhibited no relapses, whereas those with T1 not treated with PUVA had a crude relapse rate of 36%. Median DFS was not reached at 103 months for the T1 adjuvant PUVA patients versus 66 months for the non-PUVA patients (p < 0.01). For those with T2, crude relapse rates were 25% and 55%, respectively, with DFS of 60 (median DFS not reached) and 20 months (p < 0.03). The 5-year DFS for patients salvaged with PUVA was 50%. Toxicity of adjuvant and salvage PUVA therapy was acceptable, with only two patients requiring a reduction in PUVA dosage. CONCLUSION PUVA can maintain remissions in patients with CTCL after TSEBT. There is a significant benefit in DFS but no statistically significant improvement in OS. Prospective, randomized data are needed to confirm these results. PUVA is also effective as a salvage therapy after TSEBT in early-stage patients with recurrence, with acceptable toxicity.

Cisplatin, Fluorouracil, and Leucovorin Induction Chemotherapy Followed by Concurrent Cisplatin Chemoradiotherapy for Organ Preservation and Cure in Patients With Advanced Head and Neck Cancer: Long-Term Follow-Up

PURPOSE The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors. PATIENTS AND METHODS Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy. RESULTS Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment. CONCLUSION Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.

Stereotactic Body Radiotherapy for Central Lung Tumors

Introduction: Patients with centrally located lung tumors have been reported to have a higher risk of toxicity when treated with stereotactic body radiotherapy (SBRT) compared with patients with peripheral tumors. The optimal SBRT fractionation schedule for treatment of central tumors is unknown. The primary purpose of this study was to assess toxicity in patients with central lesions treated with SBRT at our institution, the majority of whom were treated with four fractions. Methods: Forty-seven patients with 51 central lesions, either primary lung cancer or lung metastases, were treated with SBRT at the Department of Therapeutic Radiology, Yale University School of Medicine/Yale Cancer Center from 2007 to 2011. The patients were treated with three to five fractions with the majority of patients receiving 50 Gy in four fractions of 12.5 Gy. Forty of the lesions were located within 2 cm of the proximal tracheobronchial tree whereas 11 were located within 2 cm of other mediastinal structures. Toxicity data were collected and analyzed according to pretreatment and tumor characteristics and dosimetric parameters. Lobar control data were compiled. Results: With a median follow-up of 11.3 months (range, 4.8–40.8), four patients experienced grade 3 dyspnea and one patient developed hemoptysis that contributed to respiratory failure and subsequent death. Grade 2 toxicity included fatigue (n = 3), dyspnea (n = 3), chest-wall pain (n = 1), and cough (n = 1). Patients with grade 3+ toxicity had larger maximum tumor diameters compared with those patients without grade 3+ toxicity (median diameter 4.3 cm versus 2.9 cm, p = 0.02). There were no detectable significant differences between the two groups with respect to baseline pulmonary function tests, distance to tracheobronchial tree, maximum point dose to the tracheobronchial tree, maximum dose to 5 cc of the tracheobronchial tree, mean lung dose, and volume of lung receiving 5 Gy, 10 Gy, and 20 Gy. There were two patients who experienced local recurrences. The median biological equivalent dose (linear quadratic formula, &agr;/&bgr; = 10) for patients with local recurrence was 76 Gy compared with 112.5 Gy for patients without local recurrence (2-tailed t test, p = 0.04). The 2-year actuarial lobar local control for the entire cohort was 94%. The 2-year lobar local-control rate for patients receiving a biological equivalent dose of 100 Gy or more was 100% and for those receiving less than 100 Gy was 80% (log rank, p = 0.02). Conclusion: SBRT for central lung tumors seems to be safe, although treatment of larger tumors does carry an increased risk of high-grade toxicity. Efforts to decrease the toxicity risk by decreasing the biologically equivalent dose resulted in increased local failure.

Surveillance Epidemiology and End Results Evaluation of the Role of Surgery for Stage I Small Cell Lung Cancer

Introduction: This study was performed to evaluate the clinical outcomes of surgery for stage I small cell lung cancer (SCLC). Methods: The National Cancer Institute Surveillance Epidemiology and End Results (SEER) database was analyzed to evaluate outcomes for patients with SCLC treated from 1988 to 2004. Patients with stage I disease were selected. Kaplan-Meier survival curves were constructed for overall survival (OS) and cause-specific survival for patient strata based on type of surgery and radiation use or nonuse. Although SEER does not provide chemotherapy details, it is assumed that most, if not all, of these patients received systemic therapy. Results: A total of 1560 patients were identified as having stage I SCLC. Median age was 70 years (range 27–94 years). Two hundred forty-seven patients underwent lobectomy, 121 had local tumor excision/ablation, 10 had a pneumonectomy, and surgery was unknown in 21. One thousand one hundred sixty-one did not have any cancer-directed surgery. Of those who had lobectomy, 205 (83%) did not receive radiation therapy (RT), 38 (15%) did receive RT, and use of RT was unknown in 4 (2%). For those who had lobectomy without RT (n = 205), 3- and 5-year OS was 58.1% (95% confidence interval [CI] 51.1–64.5%) and 50.3% (95% CI 43.1–57.1%), respectively. For those patients who had a lobectomy with RT (n = 38), 3- and 5-year OS was 64.9% (95% CI 45.5–78.9%) and 57.1% (95% CI 37.4–72.7%), respectively. Conclusions: Surgery without RT seems to offer reasonable OS outcomes in a cohort of stage I patients who undergo lobectomy. These results should be considered with the understanding that systemic therapy information and margin status are not available from the SEER database.

Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy

PURPOSE To evaluate the impact of systemic adjuvant therapies on relapse-free (RFS) and overall survival (OS) of cutaneous T-cell lymphoma (CTCL) patients treated with total skin electron beam therapy (TSEBT). METHODS AND MATERIALS Between 1974 and 1990, TSEBT (36 Gy at 1 Gy/day; 9 weeks; 6 MeV electrons) was administered with curative intent to a total of 163 CTCL (mycosis fungoides) patients using six fields supplemented by orthovoltage boosts (120 kvp, 1 Gy x 20) to the perineum, soles of feet, and apical scalp (120 kvp, 2 Gy x 3). In this group, all patients who achieved a clinical complete response or a good partial response were offered one of two competing regimens of either adjuvant doxorubicin/cyclophosphamide or adjuvant extracorporeal photochemotherapy (ECP). RESULTS When the results for the group who achieved a complete response (CR) to TSEBT were analyzed, OS for T1 and T2 patients was excellent (85-90% at 5-10 years) and not improved by either adjuvant regimen. However, T3 and T4 patients who received either adjuvant doxorubicin/cyclophosphamide (75% at 3 years) or adjuvant ECP (100% at 3 years) had better overall survival than those who received neither adjuvant regimen (approximately 50% at 5 years). The difference between the OS curves for those who received ECP vs. those who received no adjuvant therapy approached statistical significance (p < 0.06), while a significant survival benefit from the addition of chemotherapy for TSEBT complete responders was not observed. Neither adjuvant therapy provided benefit with respect to relapse free survival after TSEBT. CONCLUSIONS These results suggest that an adjuvant nontoxic regimen of extracorporeal photochemotherapy may prolong survival in advanced stage CTCL patients who have achieved a complete remission after TSEBT. The combination of doxorubicin/cyclophosphamide had no significant impact on overall survival in those patients who achieved CR to TSEBT, and neither adjuvant therapy had an impact on relapse free survival for all T-stages. Such results are the basis for the current development of a prospective, randomized trial studying the impact of ECP after TSEBT in patients with advanced stage CTCL.

Progress of Ontario's Family Health Team model: a patient-centered medical home.

Ontario’s Family Health Team (FHT) model, implemented in 2005, may be North America’s largest example of a patient-centered medical home. The model, based on multidisciplinary teams and an innovative incentive-based funding system, has been developed primarily from fee-for-service primary care practices. Nearly 2 million Ontarians are served by 170 FHTs. Preliminary observations suggest high satisfaction among patients, higher income and more gratification for family physicians, and trends for more medical students to select careers in family medicine. Popular demand is resulting in expansion to 200 FHTs. We describe the development, implementation, reimbursement plan, and current status of this multidisciplinary model, relating it to the principles of the patient-centered medical home. We also identify its potential to provide an understanding of many aspects of primary care.