Primary cutaneous lymphomas are a heterogeneous group of diseases. They often remain localized, and they generally have a more indolent course and a better prognosis than lymphomas in other ...locations. They are highly radiosensitive, and radiation therapy is an important part of the treatment, either as the sole treatment or as part of a multimodality approach. Radiation therapy of primary cutaneous lymphomas requires the use of special techniques that form the focus of these guidelines. The International Lymphoma Radiation Oncology Group has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the International Lymphoma Radiation Oncology Group steering committee on the use of radiation therapy in primary cutaneous lymphomas in the modern era.
Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging. However, immunotherapy responses are uniquely challenging to ...interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation. We hypothesized that monitoring tumor cell death in real time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy.
We compared longitudinal changes in ctDNA levels with changes in radiographic tumor size and with survival outcomes in 28 patients with metastatic non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor therapy. CtDNA was quantified by determining the allele fraction of cancer-associated somatic mutations in plasma using a multigene next-generation sequencing assay. We defined a ctDNA response as a >50% decrease in mutant allele fraction from baseline, with a second confirmatory measurement.
Strong agreement was observed between ctDNA response and radiographic response (Cohen's kappa, 0.753). Median time to initial response among patients who achieved responses in both categories was 24.5 days by ctDNA versus 72.5 days by imaging. Time on treatment was significantly longer for ctDNA responders versus nonresponders (median, 205.5 vs. 69 days;
< 0.001). A ctDNA response was associated with superior progression-free survival hazard ratio (HR), 0.29; 95% CI, 0.09-0.89;
= 0.03, and superior overall survival (HR, 0.17; 95% CI, 0.05-0.62;
= 0.007).
A drop in ctDNA level is an early marker of therapeutic efficacy and predicts prolonged survival in patients treated with immune checkpoint inhibitors for NSCLC.
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PURPOSEThis study aimed to analyze gender differences in rank, career duration, publication productivity, and research funding among radiation oncologists at U.S. academic institutions.
METHODFor 82 ...domestic academic radiation oncology departments, the authors identified current faculty and recorded their academic rank, degree, and gender. The authors recorded bibliographic metrics for physician faculty from a commercially available database (Scopus, Elsevier BV), including numbers of publications from 1996 to 2012 and h-indices. The authors then concatenated these data with National Institutes of Health (NIH) funding per Research Portfolio Online Reporting Tools. The authors performed descriptive and correlative analyses, stratifying by gender and rank.
RESULTSOf 1,031 faculty, 293 (28%) women and 738 (72%) men, men had a higher median m-index, 0.58 (range 0–3.23) versus 0.47 (0–2.5) (P < .05); h-index, 8 (0–59) versus 5 (0–39) (P < .05); and publication number, 26 (0–591) versus 13 (0–306) (P < .05). Men were more likely to be senior faculty and receive NIH funding. After stratifying for rank, these differences were largely nonsignificant. On multivariate analysis, there were correlations between gender, career duration and academic position, and h-index (P < .01).
CONCLUSIONSDeterminants of a successful career in academic medicine are multifactorial. Data from radiation oncologists show a systematic gender association, with fewer women achieving senior faculty rank. However, women achieving seniority have productivity metrics comparable to those of male counterparts. This suggests that early career development and mentorship of female faculty may narrow productivity disparities.
Prior studies have forecasted demand for radiation therapy to grow 10 times faster than the supply between 2010 and 2020. We updated these projections for 2015 to 2025 to determine whether this ...imbalance persists and to assess the accuracy of prior projections.
The demand for radiation therapy between 2015 and 2025 was estimated by combining current radiation utilization rates determined by the Surveillance, Epidemiology, and End Results data with population projections provided by the US Census Bureau. The supply of radiation oncologists was forecast by using workforce demographics and full-time equivalent (FTE) status provided by the American Society for Radiation Oncology (ASTRO), current resident class sizes, and expected survival per life tables from the US Centers for Disease Control.
Between 2015 and 2025, the annual total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 19%, from 490,000 to 580,000. Assuming a graduating resident class size of 200, the number of FTE physicians is expected to increase by 27%, from 3903 to 4965. In comparison with prior projections, the new projected demand for radiation therapy in 2020 dropped by 24,000 cases (a 4% relative decline). This decrease is attributable to an overall reduction in the use of radiation to treat cancer, from 28% of all newly diagnosed cancers in the prior projections down to 26% for the new projections. By contrast, the new projected supply of radiation oncologists in 2020 increased by 275 FTEs in comparison with the prior projection for 2020 (a 7% relative increase), attributable to rising residency class sizes.
The supply of radiation oncologists is expected to grow more quickly than the demand for radiation therapy from 2015 to 2025. Further research is needed to determine whether this is an appropriate correction or will result in excess capacity.
A 58-year-old man presents with a 2-week history of progressive dyspnea on exertion, neck swelling, decreased appetite, and fatigue. There is no history of syncope or dysphagia. He smoked cigarettes ...until 5 years ago. The physical examination reveals a heart rate of 105 beats per minute, a respiratory rate of 20 breaths per minute, and superficial vascular distention over the neck, chest, and upper abdomen. Stridor is not present. How should his case be evaluated and managed?
A 58-year-old man presents with progressive dyspnea on exertion and neck swelling. The physical examination reveals a heart rate of 105 beats per minute and superficial vascular distention over the neck, chest, and upper abdomen. How should his case be evaluated and managed?
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.
Stage
A 58-year-old man presents with a 2-week history of progressive dyspnea on exertion, neck swelling, decreased appetite, and fatigue. There is no history of syncope or dysphagia. He smoked cigarettes until 5 years ago. The physical examination reveals a heart rate of 105 beats per minute, a respiratory rate of 20 breaths per minute, and superficial vascular distention over the neck, chest, and upper abdomen. Stridor is not present. How should his case be evaluated and managed?
The Clinical Problem
The superior vena cava syndrome, which occurs in approximately 15,000 persons in the United States each year, encompasses a . . .
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.
To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of ...outcome.
The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide.
Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease.
Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.
The role of postoperative radiotherapy (PORT) after surgical resection of non–small-cell lung cancer (NSCLC) remains controversial. Although pertinent randomized evidence is lacking, historical ...studies have shown a survival detriment, partially attributed to antiquated radiotherapy techniques and supratherapeutic doses, whereas more recent nonrandomized data have suggested a survival benefit for PORT in appropriate patients. This analysis reassesses the impact of PORT in a modern cohort of patients with particular attention to radiotherapy details.
Patients treated with margin-negative (R0) surgical resection of NSCLC with complete adjuvant treatment information were identified within the National Cancer Database. Overall survival (OS) was compared between patients based upon pathologic stage of disease, histologic subtype, and details of adjuvant therapy delivered.
We identified 30,552 patients treated for stages II–IIIA NSCLC in National Cancer Database between 1998 and 2006. Histology was adenocarcinoma in 16,482, squamous cell in 9847, large cell in 1715 and other in 2562. Overall, 3430 patients (11.2%) received PORT, and 23.8% of N2 patients received PORT. There was a detriment in 5-year OS with PORT for pathologically N0 (48 versus 37.7%, p < 0.001) and N1 patients (39.4 versus 34.8%, p < 0.001), although 5-year OS was improved with PORT in N2 patients (27.8 versus 34.1%, p < 0.001). Importantly, PORT dose was found to have a significant impact on OS. Patients who received 45 to 54 Gy demonstrated superior survival relative to patients without PORT (5-year OS 38 versus 27.8%, p < 0.001), although patients who received greater than 54 Gy had equivalent survival to patients treated without PORT (5-year OS 27.6 versus 27.8%, p = 0.784). PORT with doses of 45 to 54 Gy remained significantly associated with improved OS on multivariate analysis (hazard ratio for death 0.85, 95% confidence interval 0.76–0.94, p < 0.001).
PORT delivered with modern techniques with appropriate doses continues to demonstrate a survival benefit in patients with positive mediastinal nodal metastases, and therefore should remain a standard of care for this population.
To characterize temporal trends in the application of various bone metastasis fractionations within the United States during the past decade, using the National Cancer Data Base; the primary aim was ...to determine whether clinical practice in the United States has changed over time to reflect the published randomized evidence and the growing movement for value-based treatment decisions.
The National Cancer Data Base was used to identify patients treated to osseous metastases from breast, prostate, and lung cancer. Utilization of single-fraction versus multiple-fraction radiation therapy was compared according to demographic, disease-related, and health care system details.
We included 24,992 patients treated during the period 2005-2011 for bone metastases. Among patients treated to non-spinal/vertebral sites (n=9011), 4.7% received 8 Gy in 1 fraction, whereas 95.3% received multiple-fraction treatment. Over time the proportion of patients receiving a single fraction of 8 Gy increased (from 3.4% in 2005 to 7.5% in 2011). Numerous independent predictors of single-fraction treatment were identified, including older age, farther travel distance for treatment, academic treatment facility, and non-private health insurance (P<.05).
Single-fraction palliative radiation therapy regimens are significantly underutilized in current practice in the United States. Further efforts are needed to address this issue, such that evidence-based and cost-conscious care becomes more commonplace.