Impact of Clinical Trial Design on Recruitment of Racial and Ethnic Minorities.

Knowledge related to how oncology treatment trial design influences enrollment of racial and ethnic minorities is limited. Rigorous identification of clinical trial design parameters that associate favorably with minority accrual provides educational opportunities for individuals interested in designing more representative treatment trials. We identified oncology trials with a minimum of 10 patients at an NCI-Designated Comprehensive Cancer Center from 2010 to 2021. We defined a study endpoint of racial and ethnic minority accrual greater than zero. Multivariable logistic regression was used to determine whether co-variables predicted our study endpoint. P-values of less than 0.05 were considered significant. A total of 352 cancer trials met eligibility criteria. These studies enrolled a total of 7981 patients with a total of 926 racial and ethnic minorities leading to a median enrollment of 10%. Trials open in community sites (yes versus no) were more likely to have a minority patient (OR, 2.21; 95% CI, 1.02-4.96) as well as pilot/phase I studies compared to phase II/III (OR, 3.19; 95% CI, 1.34-8.26). Trials incorporating immunotherapy (yes versus no) were less likely to have a minority patient (OR, 0.47; 95% CI, 0.23-0.94). Trials open in community sites as well as early phase treatment studies were more likely to accrue minority patients. However, studies including immunotherapy were less likely to accrue racial and ethnic minorities. Knowledge gained from our analysis may help individuals design oncology treatment trials that are representative of more diverse populations.

Long-term risk of carotid stenosis and cerebrovascular disease after radiation therapy for head and neck cancer.

BACKGROUND: Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk for carotid artery stenosis (CAS) and cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences of CAS and CVD among HNC survivors after RT and (2) whether CAS is associated with a RT dose response effect. METHODS: This single-institution retrospective cohort study examined patients with nonmetastatic HNC who completed (chemo)RT from January 2000 through October 2020 and subsequently received carotid imaging surveillance ≤2 years following RT completion and, in the absence of CAS, every 3 years thereafter. Exclusion criteria included history of known CAS/CVD. Asymptomatic CAS was defined as ≥50% reduction of luminal diameter, symptomatic CAS as stroke or transient ischemic attack, and composite CAS as asymptomatic or symptomatic CAS. RESULTS: Of 628 patients undergoing curative intent RT for HNC, median follow-up was 4.8 years (interquartile range, 2.6-8.3), with 97 patients followed ≥10 years. Median age was 61 years and 69% of patients received concurrent chemotherapy and 28% were treated postoperatively. Actuarial 10-year incidences of asymptomatic, symptomatic, and composite CAS were 29.6% (95% CI, 23.9-35.5), 10.1% (95% CI, 7.0-13.9), and 27.2% (95% CI, 22.5-32.1), respectively. Multivariable Cox models significant association between asymptomatic CAS and absolute carotid artery volume receiving ≥10 Gy (per mL: hazard ratio, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: HNC survivors are at high risk for post-RT CAS. A dose response effect was observed for asymptomatic CAS at doses as low as 10 Gy. PLAIN LANGUAGE SUMMARY: Recipients of radiation therapy for head and neck cancer are at significantly increased risk for carotid artery stenosis and cerebrovascular disease. However, carotid artery screening is not routinely performed among head and neck survivors following radiation therapy. In this single-institution retrospective cohort study, patients with head and neck cancer were initially screened for carotid artery stenosis ≤2 years following radiation therapy completion, then every 3 years thereafter. The 10-year actuarial incidence of carotid artery stenosis was >25% and stroke/transient ischemic attack >10%. Multivariable analysis demonstrated significant associations between asymptomatic carotid artery stenosis and artery volumes receiving ≥10 Gy.

Prospective Correlation of Magnetic Resonance Tumor Regression Grade With Pathologic Outcomes in Total Neoadjuvant Therapy for Rectal Adenocarcinoma.

PURPOSE: Total neoadjuvant therapy (TNT) is a newly established standard treatment for rectal adenocarcinoma. Current methods to communicate magnitudes of regression during TNT are subjective and imprecise. Magnetic resonance tumor regression grade (MR-TRG) is an existing, but rarely used, regression grading system. Prospective validation of MR-TRG correlation with pathologic response in patients undergoing TNT is lacking. Utility of adding diffusion-weighted imaging to MR-TRG is also unknown. METHODS: We conducted a multi-institutional prospective imaging substudy within NRG-GI002 (ClinicalTrials.gov identifier: NCT02921256) examining the ability of MR-based imaging to predict pathologic complete response (pCR) and correlate MR-TRG with the pathologic neoadjuvant response score (NAR). Serial MRIs were needed from 110 patients. Three radiologists independently, then collectively, reviewed each MRI for complete response (mriCR), which was tested for positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity with pCR. MR-TRG was examined for association with the pathologic NAR score. All team members were blinded to pathologic data. RESULTS: A total of 121 patients from 71 institutions met criteria: 28% were female (n = 34), 84% White (n = 101), and median age was 55 (24-78 years). Kappa scores for T- and N-stage after TNT were 0.38 and 0.88, reflecting fair agreement and near-perfect agreement, respectively. Calling an mriCR resulted in a kappa score of 0.82 after chemotherapy and 0.56 after TNT reflected near-perfect agreement and moderate agreement, respectively. MR-TRG scores were associated with pCR (P < .01) and NAR (P < .0001), PPV for pCR was 40% (95% CI, 26 to 53), and NPV was 84% (95% CI, 75 to 94). CONCLUSION: MRI alone is a poor tool to distinguish pCR in rectal adenocarcinoma undergoing TNT. However, the MR-TRG score presents a now validated method, correlated with pathologic NAR, which can objectively measure regression magnitude during TNT.

Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504.

PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown. METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms. RESULTS: Of 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had >10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol. CONCLUSIONS: Concomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593).

Anal Cancer: Emerging Standards in a Rare Disease.

The social stigma surrounding an anal cancer diagnosis has traditionally prevented open discussions about this disease. However, as recent treatment options and an increasing rate of diagnoses are made worldwide, awareness is growing. In the United States alone, 9,090 individuals were expected to be diagnosed with anal cancer in 2021. The US annual incidence of squamous cell carcinoma of the anus continues to increase by 2.7% yearly, whereas the mortality rate increases by 3.1%. The main risk factor for anal cancer is a human papillomavirus infection; those with chronic immunosuppression are also at risk. Patients with HIV are 19 times more likely to develop anal cancer compared with the general population. In this review, we have provided an overview of the carcinoma of the anal canal, the role of screening, advancements in radiation therapy, and current trials investigating acute and chronic treatment-related toxicities. This article is a comprehensive approach to presenting the existing data in an effort to encourage continuous international interest in anal cancer.

Proton Beam Therapy for Locally Advanced Head and Neck Tumors: An Analysis of Dosimetric and Clinical Outcomes.

OBJECTIVE: Locally advanced tumors of the head and neck region often lie in close proximity to critical organs at risk (OARs). Providing effective treatment coverage to these malignancies while minimizing radiation dose to surrounding OARs is advantageous. Our aim is to compare dosimetric data of OARs from proton beam therapy (PBT) plans to volumetric modulated arc therapy (VMAT) treatment plans, and to evaluate clinical outcomes in patients treated with PBT. METHODS: We identified patients with locally advanced head and neck tumors treated with PBT at our institution from 2016 to 2019. Study endpoints included mean and maximum doses for the OAR structures for each treatment plan, overall survival, time to local-regional or distant progression, and presence of acute and late toxicities. Mean and maximum doses to OAR structures were compared between treatment modalities using a paired Wilcoxon signed-rank test. P-values <0.05 were considered significant. RESULTS: A total of 42 patients were identified. Clinical target volume coverage was >95% for both PBT and VMAT plans. PBT plans showed a significant reduction to the mean doses to all OARs, and max doses to most OARs (P<0.05). The largest reduction mean dose was seen in the contralateral cochlea and parotid glands at 71% and 75%, respectively. Median follow-up was 27 months. Overall survival at 4 years was 44.75%. Freedom from local-regional progression was 73.28% at 2 years. The majority of patients developed Common Terminology Criteria for Adverse Events (CTCAE) grade I dermatitis, mucositis, or both. CONCLUSIONS: PBT resulted in meaningful dose reductions to OARs while maintaining comparable target coverage when compared with VMAT plans. Further refinements to proton therapy may have the potential to further minimize dose to critical structures.

Proton Beam Therapy in the Treatment of Periorbital Malignancies.

PURPOSE: Periorbital tumor location presents a significant challenge with 3-dimensional conformal radiation therapy or intensity modulated radiation therapy due to high tumor dose needed in the setting of close proximity to orbital structures with lower tolerance. Proton beam therapy (PBT) is felt to be an effective modality in such cases due to its sharp dose gradient. MATERIALS AND METHODS: We reviewed our institutional PBT registry and identified 17 patients with tumor epicenters within 2 cm of the eye and optic apparatus treated with passive scatter PBT with comparison volumetric arc therapy plans available. Maximum and mean doses to organs at risk of interest, including optic nerves, optic chiasm, lens, eye ball, pituitary, cochlea, lacrimal gland, and surrounding brain, were compared using the paired Wilcoxon signed rank test. Overall survival was determined using the Kaplan-Meier method. RESULTS: Median age was 67. Median follow-up was 19.7 months. Fourteen patients underwent upfront resection and received postoperative radiation and 3 received definitive radiation. One patient received elective neck radiation, 2 underwent reirradiation, and 3 had concurrent chemotherapy. There was a statistically significant reduction in mean dose to the optic nerves and chiasm, brain, pituitary gland, lacrimal glands, and cochlea as well as in the maximum dose to the optic nerves and chiasm, pituitary gland, lacrimal glands, and cochlea with PBT. The 18-month cumulative incidence of local failure was 19.1% and 1-year overall survival was 80.9%. CONCLUSION: Proton beam therapy resulted in significant dose reductions to several periorbital and optic structures compared with volumetric arc therapy. Proton beam therapy appears to be the optimal radiation modality in such cases to minimize risk of toxicity to periorbital organs at risk.

Analysis of Patient-Reported Outcome Utilization Within National Clinical Trials Network Cooperative Group Radiation Oncology Trials Over the Past 2 Decades.

PURPOSE: When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion. METHODS AND MATERIALS: This cross-sectional study analyzed the frequency of use of PROs in National Clinical Trials Network cooperative group radiation therapy phase 2 and 3 clinical trials over the past 2 decades. A literature review was performed to determine the publication outcomes of PRO data, including only trials that used PROs in their design and were mature enough to have published results. RESULTS: Fifty-seven (56.4%) of the 101 trials included in this study included PROs in their design. Brain and head and neck trials demonstrated the largest proportional incorporation of PROs (81.8% and 76.9%, respectively), and thoracic and breast trials used the fewest (18.8% and 37.5%, respectively). The EQ-5D family of questionnaires was the most commonly used PROs, used in 22.8% of trials included. The literature review demonstrated a pattern of increased publication of PRO data alongside survival endpoints in manuscripts derived from these trials over time. CONCLUSIONS: Though there is room for improvement, the field of radiation oncology has embraced the incorporation of PROs into multicenter, high-impact clinical trials over the past 2 decades and has increased its publication of this data alongside survival data from these trials.

Chemoradiotherapy-related carotid artery inflammation in head and neck cancer patients quantified by [18F]FDG PET/CT.

OBJECTIVES: Radiotherapy (RT) is associated with an increased risk of cardiovascular disease (CVD), but little is known about the mechanism for vascular injury and methods for early detection. MATERIALS AND METHODS: We conducted a prospective, pilot study of carotid artery inflammation using 18F-labeled 2-fluoro-2-deoxy-d-glucose ([18F]FDG) PET/CT imaging pre- and 3 months post-RT in head-and-neck cancer (HNC) patients. [18F]FDG uptake by the carotid arteries was measured by the maximum and mean target to background ratio (TBRMAX, TBRMEAN) and the mean partial volume corrected standardized uptake value (pvcSUVMEAN). RESULTS: Of the 22 patients who completed both pre and post-RT scans, the majority (82%) had stage III or stage IV disease and received concurrent chemotherapy. TBRMAX, TBRMEAN, and pvcSUVMEAN were all significantly higher 3 months after RT versus before RT with mean difference values (95% CI; p-value) of 0.17 (0.1-0.25; 0.0001), 0.19 (0.12-0.25; 0.0001), and 0.31 g/ml (0.12-0.5; 0.002), respectively. Fifteen patients (68%) had HPV-positive tumors, which were associated with lower pre-RT [18F]FDG signal, but a greater increase in TBRMAX (19% vs 5%), TBRMEAN (21% vs 11%) and pvcSUVMEAN (20% increase vs 3% decrease), compared to HPV negativity. CONCLUSION: There is a significant increase in carotid artery inflammation in HNC patients due to CRT that amounts to a degree that has previously been associated with higher risk for future CVD events. The subset of patients with HPV-positive tumors experienced the greatest increases in vascular inflammation due to CRT. Carotid [18F]FDG uptake may be an early biomarker of RT-related vascular injury.

The risk of carotid stenosis in head and neck cancer patients after radiation therapy.

OBJECTIVES: Head and neck radiotherapy (RT) is a risk factor for cerebrovascular disease. We performed a retrospective cohort study to evaluate carotid artery stenosis (CAS) incidence in head and neck cancer (HNC) patients undergoing RT, characterizing associated risk factors. MATERIALS AND METHODS: Records were retrospectively reviewed for HNC patients undergoing carotid ultrasound screening after definitive or adjuvant RT between January 2000 and May 2016. CAS was defined as ≥50% stenosis on imaging, stroke, or transient ischemic attack. Actuarial CAS rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses predicted CAS risk based on carotid dosimetric and clinical parameters. RESULTS: 366 patients met inclusion criteria. Median time from RT completion to last follow-up was 4.1 yr. Actuarial risk for CAS was 29% (95% CI 22-36%) at 8 years. Univariate analysis showed that smoking (HR 1.7; 95% CI 1.1-2.7), hyperlipidemia (HR 1.6; 95% CI 1.03-2.6), diabetes (HR 2.8; 95% CI 1.6-4.8), coronary artery disease (HR 2.4; 95% CI 1.4-4.2), and peripheral artery disease (HR 3.6; 95% CI 1.1-11.6) were significantly associated with increased CAS. In multivariate analysis, diabetes was predictive of time to CAS (HR 1.9; 95% CI 1.1-3.4). Carotid dose parameters were not significantly associated with CAS. CONCLUSIONS: CAS incidence is high after head and neck radiotherapy, gradually rising over time. No clear dose-response effect between carotid dose and CAS was identified for HNC patients. Carotid artery screening and preventative strategies should be employed in this high-risk patient population.

Cost-Effectiveness of Primary Radiation Therapy Versus Radical Prostatectomy for Intermediate- to High-Risk Prostate Cancer.

PURPOSE: To compare, using a cost-effectiveness analysis, the quality-adjusted life expectancy (QALE) and cost between the 2 treatment options for intermediate- to high-risk prostate cancer: (1) radiation (RT) with androgen deprivation therapy (ADT) or (2) radical prostatectomy (RP) followed by adjuvant RT for patients with risk factors. METHODS AND MATERIALS: Our Markov model allowed patients to transition between health states with yearly probabilities of developing cancer recurrence and/or toxicity. Probabilities were assigned according to favorable intermediate, unfavorable intermediate, or high-risk prostate cancer groups. The primary analysis examined outcomes for patients aged 65 years, whereas secondary analyses explored the effects of younger age, elevated baseline cardiovascular risk, and the use of salvage therapy. One-way and probabilistic sensitivity analyses were performed. RESULTS: Across all primary and secondary analyses, and using a wide-range of assumptions, RT + ADT was the preferred treatment strategy for men with intermediate- to high-risk prostate cancer. The QALE was higher after RT + ADT by 0.5 to 1.14 quality-adjusted life years, compared with RP. Radiation plus ADT was cost-effective in all situations, falling beneath a threshold of $100,000 per quality-adjusted life year. Among all risk groups, a greater proportion of patients undergoing RP experienced single or multiple treatment toxicities. CONCLUSIONS: Radiation plus ADT may result in improved QALE compared with RP for intermediate- to high-risk prostate cancer. Although biochemical failure is similar between treatment groups, there is a higher rate of developing multiple toxicities among patients treated with upfront RP.

Cardiovascular risk and prevention in patients with head and neck cancer treated with radiotherapy.

BACKGROUND: The underlying contributors to cardiovascular disease (CVD) in patients with head and neck squamous cell carcinoma (HNSCC) are poorly characterized. METHODS: Patients with HNSCC who underwent definitive or adjuvant (chemo)radiation between 2011 and 2013 were retrospectively reviewed. The 10-year risk estimates for a CVD event were calculated according to the Framingham Risk Score (FRS). RESULTS: One hundred fifteen patients with predominantly stage III/IV HNSCC had a median follow-up of 2 years. At diagnosis, 23% of patients had CVD. The FRS was higher among patients with laryngeal cancer versus other sites (20.5% vs 14.4%). Twenty-four percent of all patients had uncontrolled blood pressure at diagnosis. Among the patients with CVD, 41% were not taking antiplatelet therapy and 30% were not taking statin therapy. Thirty-four percent of patients without CVD had indications for initiating statin therapy. CONCLUSION: Patients with HNSCC have a high baseline CVD risk and many do not receive optimal preventive care. © 2016 Wiley Periodicals, Inc. Head Neck 39: 527-532, 2017.

Stereotactic body radiotherapy for pancreatic cancer: recent progress and future directions.

Despite advances in surgical, medical, and radiation therapy for pancreatic cancer, the prognosis remains poor. At this time, the only chance for long-term survival is surgical resection. More challenging is the optimal management of unresectable locally advanced pancreatic cancer, which has historically been treated with concurrent chemoradiation or chemotherapy alone. However, the survival and local control benefit of conventional radiotherapy in addition to chemotherapy was unclear. More recently, stereotactic body radiotherapy (SBRT) is emerging as a viable approach to maximizing local tumor control with a tolerable side effect profile. SBRT achieves sharp dose fall-off facilitating safe delivery of highly focused radiation to the tumor over 1-5 days. Although the optimal regimen of pancreas SBRT has not yet been established, its short treatment course limits the delay of additional. Future directions involve prospective study of pancreas SBRT and exploration of biomarkers and imaging technology in order to adopt a personalized management paradigm.

Adjuvant and neoadjuvant options in resectable gastric cancer: is there an optimal treatment approach?

Gastric cancer is one of the most prevalent and deadliest forms of cancer worldwide. Even though neoadjuvant, perioperative, and adjuvant chemotherapy and/or radiation therapy may improve outcomes compared with surgery alone, the optimal combination of treatment modalities remains controversial. While European and North American trials established perioperative chemotherapy and adjuvant chemoradiation regimens for gastric cancer, Asian countries have focused on the use of adjuvant chemotherapy. This review summarizes results from contemporary randomized controlled trials and meta-analyses to elucidate the relative merits of each treatment approach.

Stereotactic body radiotherapy: an effective local treatment modality for hepatocellular carcinoma.

Although liver-directed therapies such as surgery or ablation can cure hepatocellular carcinoma, few patients are eligible due to advanced disease or medical comorbidities. In advanced disease, systemic therapies have yielded only incremental survival benefits. Historically, radiotherapy for liver cancer was dismissed due to concerns over unacceptable toxicities from even moderate doses. Although implementation requires more resources than standard radiotherapy, stereotactic body radiotherapy can deliver reproducible, highly conformal ablative radiotherapy to tumors while minimizing doses to nearby critical structures. Trials of stereotactic body radiotherapy for hepatocellular carcinoma have demonstrated promising local control and survival results with low levels of toxicity in Child-Pugh class A patients. We review the published literature and make recommendations for the future of this emerging modality.

Patterns of recurrence after trimodality therapy for esophageal cancer.

BACKGROUND: Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined. METHODS: All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery. RESULTS: Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%). CONCLUSIONS: Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes.

Incidence and risk factors of significant carotid artery stenosis in asymptomatic survivors of head and neck cancer after radiotherapy.

BACKGROUND: The incidence and risk factors of carotid artery stenosis in asymptomatic patients after head and neck radiation therapy (RT) are unknown. METHODS: This retrospective study reviewed asymptomatic patients treated with RT for head and neck cancer from 2000 to 2009 who underwent screening carotid ultrasound. RESULTS: Two hundred twenty-four patients were included, the majority of whom had stage III to IV disease and received cisplatin-based chemotherapy. Median time from RT completion to last carotid ultrasound was 3 years. Actuarial rate of carotid artery stenosis at 4 years was 14% (95% confidence interval [CI], 4% to 22%). Multivariate analysis revealed that carotid artery stenosis was associated with Framingham risk factors (hazard ratio [HR], 1.6 per factor; 95% CI, 1.2-2.2; p = .003). Among 135 patients treated with intensity-modulated radiation therapy (IMRT), the HR for carotid artery stenosis was 1.4 for every 10 Gy increase in mean RT dose to the carotid bulb plus 2 cm (95% CI, 0.8-2.4; p = .35). CONCLUSION: Prevention and screening programs should be considered for head and neck cancer survivors given the high risk of carotid artery stenosis.

Radiotherapy dose-response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy.

OBJECTIVE: To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). METHODS: Patients with stage I-IV DLBCL treated from 1995-2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. RESULTS: 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12-40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p < 0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites ≥ 10 cm (14% versus 4%, p = 0.06). CONCLUSION: In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response.

Impact of consolidation radiation therapy in stage III-IV diffuse large B-cell lymphoma with negative post-chemotherapy radiologic imaging.

PURPOSE: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. METHODS AND MATERIALS: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. RESULTS: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). CONCLUSIONS: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.