Laying the Foundation for a Mesothelioma Patient Registry: Development of Data Collection Tools.

Mesothelioma, a cancer of mesothelial cells that line the chest, lungs, heart, and abdomen, is a relatively rare disease. In the United States, approximately 3000 individuals are diagnosed with mesothelioma annually. The primary risk factor for mesothelioma is occupational asbestos exposure which can occur decades prior to disease development, though in approximately 20% of cases, known asbestos exposure is lacking. While several other countries have developed mesothelioma registries to collect key clinical and exposure data elements to allow better estimation of incidence, prevalence, and risk factors associated with disease development, no national mesothelioma registry exists in the U.S. Therefore, as part of a larger feasibility study, a patient exposure questionnaire and a clinical data collection tool were created using a series of key informant interviews. Findings suggest that risk factor and clinical data collection via an on-line questionnaire is feasible, but specific concerns related to confidentiality, in the context of employer responsibility for exposure in the unique U.S. legal environment, and timing of enrollment must be addressed. Lessons learned from piloting these tools will inform the design and implementation of a mesothelioma registry of national scope.

Assessing Outcomes of Patients Treated With Re-Irradiation Utilizing Proton Pencil-Beam Scanning for Primary or Recurrent Malignancies of the Esophagus and Gastroesophageal Junction.

INTRODUCTION: Re-irradiation (re-RT) for locoregionally recurrent esophageal and gastroesophageal junction (GEJ) cancer and de novo esophageal + GEJ cancer arising in-field after a course of prior radiation poses considerable treatment challenges given the sensitivity of surrounding organs at risk (OARs). Guidelines for treatment of this presentation are not well established. Pencil-beam scanning (PBS) proton therapy has the ability to decrease radiation dose to OARs relative to photon plans. We present the first published series to date of re-RT with PBS for esophageal + GEJ malignancies and hypothesize that re-RT with proton PBS will be feasible and improve the safety profile of re-RT for this cohort of patients. METHODS: Consecutive esophageal + GEJ cancers treated with PBS re-RT within a single institution were analyzed. Comparative volumetric-modulated arc therapy photon plans were generated. A total of 17 patients were included for analysis. RESULTS: At a median follow-up of 11.6 months, 1-year local control was 75.3% and overall survival was 68.9%. There were five (27.8%) grade 3 or higher late toxicities. When matched for clinical target volume coverage, proton PBS plans delivered significantly lower doses to the spinal cord, lungs, liver, and heart (all p < 0.05); five volumetric-modulated arc therapy plans would have been undeliverable on the basis of physician-specified OAR constraints. CONCLUSIONS: Re-RT for de novo or recurrent malignancies of the esophagus + GEJ, when delivered with PBS proton therapy, yields high rates of local control with acceptable acute and late toxicities in a high-risk population and decreased radiation dose to OARs relative to comparative photon plans. This is the largest series of proton re-RT for esophageal malignancies and the first that exclusively used PBS.

Clinical Outcomes of Patients With Recurrent Lung Cancer Reirradiated With Proton Therapy on the Proton Collaborative Group and University of Florida Proton Therapy Institute Prospective Registry Studies.

PURPOSE: We sought to assess clinical outcomes and toxicities of patients with recurrent lung cancer reirradiated with proton beam therapy (PBT) who were enrolled in 2 prospective registry trials. METHODS AND MATERIALS: Seventy-nine consecutive patients were reirradiated with PBT at 8 institutions. Conventionally fractionated radiation therapy was used to treat the previous lung cancer in 68% of patients (median equivalent dose in 2 Gy fractions [EQD2], 60.2 Gy) and hypofractionated/stereotactic body radiation therapy in 32% (median EQD2, 83.3 Gy). Nine patients (11%) received ≥2 courses of thoracic irradiation before PBT. Eastern Cooperative Oncology Group (ECOG) performance status was 2 to 3 in 13%. Median time from prior radiation therapy to PBT was 19.9 months. PBT was delivered with conventional fractionation in 58% (median EQD2, 60 Gy), hyperfractionation in 3% (median EQD2, 62.7 Gy), and hypofractionation in 39% (median EQD2, 60.4 Gy). Twenty-four patients (30%) received chemotherapy concurrently with PBT. RESULTS: All patients completed PBT as planned. At a median follow-up of 10.7 months after PBT, median overall survival (OS) and progression-free survival (PFS) were 15.2 months and 10.5 months, respectively. Acute and late grade 3 toxicities occurred in 6% and 1%, respectively. Three patients died after PBT from possible radiation toxicity. On multivariate analysis, ECOG performance status ≤1 was associated with OS (hazard ratio, 0.35; 95% confidence interval, 0.15-0.80; P = .014) and PFS (hazard ratio, 0.32; 95% confidence interval, 0.14-0.73; P = .007). CONCLUSIONS: This is the largest series to date of PBT reirradiation for recurrent lung cancer and indicates that reirradiation with PBT is well tolerated with acceptable toxicity and encouraging efficacy. ECOG performance status was associated with OS and PFS.

Combining immunotherapy with radiation therapy in thoracic oncology.

Thoracic malignancies comprise some of the most common and deadly cancers. Immunotherapies have been proven to improve survival outcomes for patients with advanced non-small cell lung cancer (NSCLC) and show great potential for patients with other thoracic malignancies. Radiation therapy (RT), an established and effective treatment for thoracic cancers, has acted synergistically with immunotherapies in preclinical studies. Ongoing clinical trials are exploring the clinical benefits of combining RT with immunotherapies and the optimal manner in which to deliver these complementary treatments.

Proton beam therapy for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare disease with a poor prognosis. Surgical techniques have made incremental improvements over the last few decades while new systemic therapies, including immunotherapies, show promise as potentially effective novel therapies. Radiation therapy has historically been used only in the palliative setting or as adjuvant therapy after extrapleural pneumonectomy, but recent advances in treatment planning and delivery techniques utilizing intensity-modulated radiation therapy and more recently pencil-beam scanning (PBS) proton therapy, have enabled the delivery of radiation therapy as neoadjuvant or adjuvant therapy after an extended pleurectomy and decortication or as definitive therapy for patients with recurrent or unresectable disease. In particular, PBS proton therapy has the potential to deliver high doses of irradiation to the entire effected pleura while significantly reducing doses to nearby organs at risk. This article describes the evolution of radiation therapy for MPM and details how whole-pleural PBS proton therapy is delivered to patients at the Maryland Proton Treatment Center.

Utilization of Intensity-Modulated Radiation Therapy for Malignant Pleural Mesothelioma in the United States.

BACKGROUND: Although postoperative radiotherapy (RT) for malignant pleural mesothelioma (MPM) has historically been delivered using 3-dimensional conformal RT (3DCRT) techniques, multiple reports show noteworthy safety and efficacy of the more advanced intensity-modulated RT (IMRT). To our knowledge, this is the only known study to evaluate national practice patterns of IMRT utilization for MPM. MATERIALS AND METHODS: The National Cancer Data Base was queried for newly-diagnosed MPM patients who underwent definitive surgery (extrapleural pneumonectomy [EPP] or extended pleurectomy/decortication [P/D]) followed by adjuvant RT. Patients with metastatic disease, non-EPP or P/D surgical techniques, and lack of RT receipt (or without specified RT technique) were excluded. Statistics included multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis, and Cox proportional hazards modeling. RESULTS: Overall, 286 patients met criteria (181 [63%] IMRT and 105 [37%] 3DCRT). Temporal trends revealed that although 3DCRT was more common at initial time periods, IMRT utilization rose from 2004 to 2007 and stayed as a relatively constant majority thereafter. This was also present when substratifying the cohort according to EPP versus P/D approaches. IMRT was more often delivered at academic centers, along with institutions in the Southern United States, whereas 3DCRT was more frequently utilized in community facilities and in the Northeast (P ≤ .05 for all). RT technique did not affect OS (P > .05 for all comparisons). CONCLUSION: In the United States, IMRT is now the most commonly utilized adjuvant RT technique for MPM. Facility and regional differences might associate with IMRT delivery. The findings of this investigation have implications for insurance coverage, clinical referral patterns, and ongoing and future prospective trial design.

Evaluation of chemotherapy-induced peripheral neuropathy using current perception threshold and clinical evaluations.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is increasing with introduction of new and combination cancer pharmacotherapies. This study evaluated associations between clinical and self-report measurements and current perception threshold (CPT), a neuroselective measure of sensory nerve function that may detect asymptomatic CIPN damage. METHODS: Data for this secondary analysis were from a prospective, observational study using CPT to evaluate CIPN. Bivariate mixed models, accounting for the intraclass correlation between repeated patient assessments, were used to assess the relationship between CPT at each frequency (5, 250, and 2,000 Hz) and each subjective measure (Neuropathic Pain Scale, FACT-GOGntx) and objective measurement (quantitative sensory testing, deep tendon reflexes, and grip strength). RESULTS: A total of 29 chemotherapy-naïve subjects with various cancer types had a mean age of 56.7 (SD 10.4); nine subjects developed CIPN grade >1 using NCI CTC-AE criteria. Cold detection thresholds were inversely associated with CPT 5 [b(95 % CI) = -2.5(-4.5, -0.5)] and CPT 2,000 [-7.5(-11.8, -3.3)] frequencies. FACT GOG-ntx quality of life (QoL) scale and neurotoxicity and function subscales were inversely associated with CPT 2,000 [-1.8 (-3.5, -0.05), -2.2 (-4.2, -0.2), and -5.4 (-9.8, -0.9), respectively], indicating worsening QoL, impairment, and function as hypoesthesia increases. CONCLUSIONS: CPT 2,000 may identify impending worsening of patient-reported outcomes such as QoL.

Histone deacetylase inhibitors: novel agents in cancer treatment.

Histone deacetylase inhibitors (HDAC-Is) are agents that have demonstrated anticancer activity in vivo and in vitro, leading to clinical trials evaluating their efficacy in multiple cancer types. Only two HDAC-Is are currently approved by the U.S. Food and Drug Administration, vorinostat and romidepsin, both with indications for cutaneous T-cell lymphoma. Romidepsin has an additional approval in peripheral T-cell lymphoma. Promising clinical trial results in other cancer types will likely lead to expanded use of these and other HDAC-Is. To provide care for patients receiving these agents, oncology nurses should be knowledgeable about the emerging role of HDAC-Is. This article reviews the mechanism of action of HDAC-Is, currently approved therapies, and nursing management of cutaneous T-cell lymphoma.