Low grade, indolent lymphomas of the head and neck: Comparative toxicity of standard versus very low dose radiation therapy.

National Comprehensive Cancer Network guidelines recommend radiation therapy (RT) for localized indolent non-Hodgkin lymphomas (iNHL). Many referring physicians avoid RT to the head and neck (HN) due to fears of toxicity. Very low-dose radiation (4 Gy) for select patients produces sustained local control and recently gained popularity. We compared early and late toxicities of standard 24-30 Gy to 4 Gy in patients with HN iNHL. We retrospectively analyzed 266 consecutive patients with HN iNHL receiving RT from 1994 to 2017. Patient characteristics, outcomes, and toxicities were collected from medical records. Early (≤2 months post-RT) and late (>2 months post-RT) toxicities were graded per Common Terminology Criteria for Adverse Events version 4. Grades 1-2 were defined as "low-grade" and 3-4 "high-grade." Toxicity incidence was compared between 4 and >4 Gy, grouped by treated site (orbit, nonorbital head, neck, skin) and early versus late. Median follow-up was 23 months (2-145) and 68 months (2-256) for 4Gy and >4 Gy cohorts, respectively. Median dose for the >4 Gy cohort was 30 Gy (10.5-54 Gy). Early and late toxicity incidences were lower in the 4 Gy cohort compared to >4 Gy across all RT-sites: early toxicity, orbit, 42% versus 96%; nonorbital head, 24% versus 96%; neck, 22% versus 94%; skin, 31% versus 87%; late toxicity, orbit, 20% versus 71%; nonorbital head, 6% versus 66%; neck, 6% versus 57%; skin, 0% versus 46% (4 Gy vs. >4 Gy, respectively). Toxicities among both cohorts were largely low-grade. High-grade early and late toxicities did not occur in the 4 Gy cohort. There was 1 high-grade early toxicity (Grade 3 dry mouth) and 17 high-grade late toxicities (Grade 3 cataracts) in the >4 Gy cohort. RT to HN for iNHL is associated with minimal short- and long-term toxicity and excellent local control among 4 Gy and >4 Gy treatments. In this setting, "toxicity" concerns should not deter oncologists from potentially curative RT. In select patients where toxicity remains a concern, very low dose 4 Gy could be considered.

Impact of delays in definitive treatment on overall survival: a National Cancer Database study of patients with Hodgkin lymphoma.

The purpose of this large observational study was to examine outcomes in patients with Hodgkin lymphoma (HL) by timing to definitive chemotherapy (TTC) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998-2011, 56,457 patients with stage I-IV HL were studied, with a median follow-up of 6.0 years (median age=39). Median TTC was 26 days from diagnosis. The cohort of "early" (<60 days from diagnosis) TTC patients included 45,307 (80.3%) patients and "late" (≥60 days) TTC was 11,150 (19.7%). Patients were more likely to experience early TTC if they were of a younger age, at an advanced stage, with "B" symptoms, favorably insured, favorable socioeconomic status, and treated at comprehensive cancer center (all p<0.05). Ten-year overall survival for patients with early TTC was 73.2% vs. 70.0% for those with late TTC (HR=0.87; 95%CI, 0.83-0.92, p<0.0001). After PS-matching for co-variates, early TTC was not associated with overall survival (HR=0.96; 95%CI, 0.85-1.08, p=0.51). This represents the only study to evaluate overall survival by time to definitive treatment for HL.

Association of intensity-modulated radiation therapy on overall survival for patients with Hodgkin lymphoma.

PURPOSE: The purpose of this study was to compare outcomes with Hodgkin lymphoma (HL) patients receiving IMRT (intensity-modulated radiation therapy), versus those receiving 2D/3D-CRT (3-dimensional conformal RT) in a large observational cohort. PATIENTS AND METHODS: We evaluated patients diagnosed with stage I-IV HL from 1998 to 2011 from the National Cancer Database (NCDB). The association between IMRT use vs. 2D/3D-CRT, co-variables, and outcome was assessed in a Cox proportional hazards model. Propensity score (PS) matching was performed to balance known confounding factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 76,672 patients with HL within the NCDB, 12,393 patients with stage I-IV HL received RT (median dose=30.6 Gy) and were eligible for this study, and 6013 patients analyzed for overall survival. The cohort had a median follow-up of 6.2 years and median age of 37 years (range: 18-90). The RT modalities used were: 2D/3D-CRT (n=11,491, 92.7%) or IMRT (n=902, 7.3%). Patients were more likely to receive IMRT if they were of male gender, early stage, no "B" symptoms, and treated at comprehensive cancer programs (all p<0.05). During this time period, there was a significant decrease in use of 2D/3D-CRT from 100% to 81.5%, with a subsequent increase in IMRT utilization from 0% to 18.5%. Five-year overall survival for patients receiving 2D/3D-CRT (n=5844) was 89.9% versus 95.2% for those receiving IMRT (n=169; HR=0.45; 95% CI, 0.23-0.91, p=0.02). After PS-matching based on clinicopathologic characteristics, IMRT use remained associated with improved overall survival (HR=0.40; 95% CI, 0.16-0.97, p=0.04). CONCLUSIONS: Our study reveals that HL patients receiving modern RT techniques were associated with an improvement in overall survival. This may have been related to patient selection, access to improved staging and management, or improvements in treatment technology. This represents the only study examining survival outcomes of advanced RT modalities, which may be considered on a case-by-case basis for highly selected patients with HL.

Coronary artery disease after radiation therapy for Hodgkin's lymphoma: coronary CT angiography findings and calcium scores in nine asymptomatic patients.

OBJECTIVE: Long-term survivors of Hodgkin's lymphoma treated with radiation therapy have an increased incidence of coronary artery disease. The purpose of this study is to describe the coronary CT angiography findings and calcium scores of asymptomatic patients who had mediastinal irradiation for Hodgkin's lymphoma and to evaluate the impact of coronary CT angiography on patient management. MATERIALS AND METHODS: We evaluated nine consecutive patients, age range 35-60 years, who had been treated for Hodgkin's lymphoma by radiation therapy between the ages of 11 and 27 years. The total mediastinal dose ranged from 34 to 45 Gy. All patients were evaluated with 64-MDCT with calcium scoring followed by CT angiography of the coronary arteries. Imaging findings and clinical follow-up were analyzed. RESULTS: Eight of nine patients had coronary artery disease. CT showed long segments of diffuse disease; areas of stenosis from soft plaque; and calcification in the proximal right coronary, left anterior descending, and left circumflex arteries. Calcium scores were significantly higher than in other patients of this age group. Additional tests, including selective coronary angiography, were necessary in patients with diffuse disease with calcifications. CT evaluation led to bypass surgery and angioplasty in two patients. CONCLUSION: Coronary CT angiography and calcium scores are useful tools for evaluation of irradiation-related coronary artery disease. Complementary tests might be necessary in selected patients. Prospective larger studies are needed to better define the role of coronary CT angiography and calcium scores and to establish an algorithm for evaluation and treatment of these patients.

NCCN task force report: positron emission tomography (PET)/computed tomography (CT) scanning in cancer.

The use of positron emission tomography (PET) is increasing rapidly in the United States, with the most common use of PET scanning related to oncology. It is especially useful in the staging and management of lymphoma, lung cancer, and colorectal cancer, according to a panel of expert radiologists, surgeons, radiation oncologists, nuclear medicine physicians, medical oncologists, and general internists convened in November 2006 by the National Comprehensive Cancer Network. The Task Force was charged with reviewing existing data and developing clinical recommendations for the use of PET scans in the evaluation and management of breast cancer, colon cancer, non-small cell lung cancer, and lymphoma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, possible future developments, and the role of PET in oncology.