Smoking and Radiation-induced Skin Injury: Analysis of a Multiracial, Multiethnic Prospective Clinical Trial.

INTRODUCTION: Smoking during breast radiotherapy (RT) may be associated with radiation-induced skin injury (RISI). We aimed to determine if a urinary biomarker of tobacco smoke exposure is associated with increased rates of RISI during and after breast RT. PATIENTS AND METHODS: Women with Stage 0-IIIA breast cancer treated with breast-conserving surgery or mastectomy followed by RT to the breast or chest wall with or without regional nodal irradiation were prospectively enrolled on a multicenter study assessing acute/late RISI. 980 patients with urinary cotinine (UCot) measurements (baseline and end-RT) were categorized into three groups. Acute and late RISI was assessed using the ONS Acute Skin Reaction scale and the LENT-SOMA Criteria. RESULTS: Late Grade 2+ and Grade 3+ RISI occurred in 18.2% and 1.9% of patients, respectively-primarily fibrosis, pain, edema, and hyperpigmentation. Grade 2+ late RISI was associated with UCot group (P= 006). Multivariable analysis identified UCot-based light smoker/secondhand smoke exposure (HR 1.79, P= .10) and smoking (HR 1.60, p = .06) as non-significantly associated with an increased risk of late RISI. Hypofractionated breast RT was associated with decreased risk of late RISI (HR 0.51, P=.03). UCot was not associated with acute RISI, multivariable analysis identified race, obesity, RT site/fractionation, and bra size to be associated with acute RISI. CONCLUSIONS: Tobacco exposure during breast RT may be associated with an increased risk of late RISI without an effect on acute toxicity. Smoking cessation should be encouraged prior to radiotherapy to minimize these and other ill effects of smoking.

Effect of Electronic Symptom Monitoring on Patient-Reported Outcomes Among Patients With Metastatic Cancer: A Randomized Clinical Trial.

Importance: Electronic systems that facilitate patient-reported outcome (PRO) surveys for patients with cancer may detect symptoms early and prompt clinicians to intervene. Objective: To evaluate whether electronic symptom monitoring during cancer treatment confers benefits on quality-of-life outcomes. Design, Setting, and Participants: Report of secondary outcomes from the PRO-TECT (Alliance AFT-39) cluster randomized trial in 52 US community oncology practices randomized to electronic symptom monitoring with PRO surveys or usual care. Between October 2017 and March 2020, 1191 adults being treated for metastatic cancer were enrolled, with last follow-up on May 17, 2021. Interventions: In the PRO group, participants (n = 593) were asked to complete weekly surveys via an internet-based or automated telephone system for up to 1 year. Severe or worsening symptoms triggered care team alerts. The control group (n = 598) received usual care. Main Outcomes and Measures: The 3 prespecified secondary outcomes were physical function, symptom control, and health-related quality of life (HRQOL) at 3 months, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference [MCID], 2-7 for physical function; no MCID defined for symptom control or HRQOL). Results on the primary outcome, overall survival, are not yet available. Results: Among 52 practices, 1191 patients were included (mean age, 62.2 years; 694 [58.3%] women); 1066 (89.5%) completed 3-month follow-up. Compared with usual care, mean changes on the QLQ-C30 from baseline to 3 months were significantly improved in the PRO group for physical function (PRO, from 74.27 to 75.81 points; control, from 73.54 to 72.61 points; mean difference, 2.47 [95% CI, 0.41-4.53]; P = .02), symptom control (PRO, from 77.67 to 80.03 points; control, from 76.75 to 76.55 points; mean difference, 2.56 [95% CI, 0.95-4.17]; P = .002), and HRQOL (PRO, from 78.11 to 80.03 points; control, from 77.00 to 76.50 points; mean difference, 2.43 [95% CI, 0.90-3.96]; P = .002). Patients in the PRO group had significantly greater odds of experiencing clinically meaningful benefits vs usual care for physical function (7.7% more with improvements of ≥5 points and 6.1% fewer with worsening of ≥5 points; odds ratio [OR], 1.35 [95% CI, 1.08-1.70]; P = .009), symptom control (8.6% and 7.5%, respectively; OR, 1.50 [95% CI, 1.15-1.95]; P = .003), and HRQOL (8.5% and 4.9%, respectively; OR, 1.41 [95% CI, 1.10-1.81]; P = .006). Conclusions and Relevance: In this report of secondary outcomes from a randomized clinical trial of adults receiving cancer treatment, use of weekly electronic PRO surveys to monitor symptoms, compared with usual care, resulted in statistically significant improvements in physical function, symptom control, and HRQOL at 3 months, with mean improvements of approximately 2.5 points on a 0- to 100-point scale. These findings should be interpreted provisionally pending results of the primary outcome of overall survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03249090.

Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424.

PURPOSE: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). METHODS AND MATERIALS: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. RESULTS: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P < .001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. CONCLUSIONS: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial.

PURPOSE: Although topical agents are often provided during radiation therapy, there is limited consensus and evidence for their use prophylactically to prevent or reduce radiation dermatitis. METHODS: This was a multi-site, randomized, placebo-controlled, blinded study of 191 breast cancer patients to compare the prophylactic effectiveness of three topical agents (Curcumin, HPR Plus™, and Placebo) for reducing radiation dermatitis and associated pain. Patients applied the topical agent to their skin in the radiation area site three times daily starting the first day of radiation therapy (RT) until 1 week after RT completion. RESULTS: Of the 191 randomized patients, 171 patients were included in the final analyses (87.5% white females, mean age = 58 (range = 36-88)). Mean radiation dermatitis severity (RDS) scores did not significantly differ between study arms (Curcumin = 2.68 [2.49, 2.86]; HPR Plus™ = 2.64 [2.45, 2.82]; Placebo = 2.63 [2.44, 2.83]; p = 0.929). Logistic regression analyses showed that increased breast field separation positively correlated with increased radiation dermatitis severity (p = 0.018). In patients with high breast field separation (≥ 25 cm), RDS scores (Curcumin = 2.70 [2.21, 3.19]; HPR Plus™ = 3.57 [3.16, 4.00]; Placebo = 2.95 [2.60, 3.30]; p = 0.024) and pain scores (Curcumin = 0.52 [- 0.28, 1.33]; HPR Plus™ = 0.55 [- 0.19, 1.30]; Placebo = 1.73 [0.97, 2.50]; p = 0.046) significantly differed at the end of RT. CONCLUSIONS: Although there were no significant effects of the treatment groups on the overall population, our exploratory subgroup analysis suggests that prophylactic treatment with topical curcumin may be effective for minimizing skin reactions and pain for patients with high breast separation (≥ 25 cm) who may have the worst skin reactions.

Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population.

Purpose This study examined an inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), in radiotherapy (RT)-induced early adverse skin reactions or toxicities in breast cancer. Patients and Methods Between 2011 and 2013, 1,000 patients with breast cancer who underwent RT were evaluated prospectively for skin toxicities through the National Cancer Institute-funded Wake Forest University Community Clinical Oncology Program Research Base. Pre- and post-RT plasma hsCRP levels and Oncology Nursing Society skin toxicity criteria (0 to 6) were used to assess RT-induced skin toxicities. Multivariable logistic regression analyses were applied to ascertain the associations between hsCRP and RT-induced skin toxicities after adjusting for potential confounders. Results The study comprised 623 white, 280 African American, 64 Asian/Pacific Islander, and 33 other race patients; 24% of the patients were Hispanic, and 47% were obese. Approximately 42% and 15% of patients developed RT-induced grade 3+ and 4+ skin toxicities, respectively. The hsCRP levels differed significantly by race and body mass index but not by ethnicity. In multivariable analysis, grade 4+ skin toxicity was significantly associated with obesity (odds ratio [OR], 2.17; 95% CI, 1.41 to 3.34], post-RT hsCRP ≥ 4.11 mg/L (OR, 1.61; 95% CI, 1.07 to 2.44), and both factors combined (OR, 3.65; 95% CI, 2.18 to 6.14). Above-median post-RT hsCRP (OR, 1.93; 95% CI, 1.03 to 3.63), and change in hsCRP (OR, 2.80; 95% CI, 1.42 to 5.54) were significantly associated with grade 4+ skin toxicity in nonobese patients. Conclusion This large prospective study is the first to our knowledge of hsCRP as an inflammatory biomarker in RT-induced skin toxicities in breast cancer. We demonstrate that nonobese patients with elevated RT-related change in hsCRP levels have a significantly increased risk of grade 4+ skin toxicity. The outcomes may help to predict RT responses and guide decision making.

Combination of post-operative radiotherapy and cetuximab for high-risk cutaneous squamous cell cancer of the head and neck: A propensity score analysis.

OBJECTIVES: The objective of this study was to investigate the safety, tolerability and preliminary efficacy of radiotherapy plus cetuximab in high risk CSCC patients. MATERIALS AND METHODS: Patients with high-risk CSCC diagnosed between 2006 and 2013 were analyzed. Patients were divided into two groups: radiotherapy alone versus radiotherapy plus cetuximab. Among 68 patients meeting study criteria, we identified 29 treated with cetuximab plus RT and 39 with RT alone. Primary analysis examined disease-free and overall survival, freedom from local and distant recurrence in the propensity score matched cohort. Propensity score analysis was performed with weighted factors including: Charlson Comorbidity Index score, age. KPS, primary location, T and N stage, recurrent status, margin status, LVSI, PNI and grade. Toxicity was assessed using the CTCAE v4.0. RESULTS: Median follow-up for living patients was 30 months. Patients in the cetuximab group were more likely to have advanced N stage, positive margins and recurrent disease. After propensity score matching the groups were well balanced. Six patients experienced ≥ grade 3 acute toxicity in the cetuximab group. The 1-year, 2-year and 5-year progression free survival (PFS) for patients in the cetuximab group were 86%, 72% and 66%, respectively. The 1-year, 2-year and 5-year overall survival (OS) for patients in the cetuximab group was 98%, 80% and 80%, respectively. CONCLUSIONS: Although limited by small numbers, the combination of cetuximab and radiotherapy in CSCC appears well tolerated there were more long-term survivors and less distant metastasis in the cetuximab group. These promising finding warrant further studies.

Updates in the Treatment of Breast Cancer with Radiotherapy.

Breast-conserving therapy is one of the most remarkable achievements of modern cancer care. The authors review the evidence supporting the role of adjuvant radiotherapy as the standard of care for breast cancer after breast-conserving surgery, consensus guidelines for margins in invasive cancer disease and ductal carcinoma in situ, the role of partial-breast irradiation and hypofractionated whole-breast irradiation, and the evolving indications for postmastectomy radiation therapy and extent of nodal coverage. Areas of research include specific methods of partial-breast irradiation, interactions between neoadjuvant chemotherapy and radiotherapy, and integration of molecular profiles with the selection of the best treatment modality and timing.

Prostate implant dosimetric outcomes and migration patterns between bio-absorbable coated and uncoated brachytherapy seeds.

PURPOSE: To evaluate the lung and pelvic seed migration and intraprostatic dose variability for prostate seed implant (PSI) using bio-absorbable polymer "coated" seeds for intraoperative planning. METHODS AND MATERIALS: A total of 100 PSI patients were initially implanted with uncoated I-125 (STM 1251 or I125-SL, N = 85) or Pd-103 (mod 200, N = 15) seeds, and 105 PSI patients were implanted subsequently with coated seeds using inverse optimization with real-time planning. Implant technique, average number of needles, and dose objectives remained identical among the cohorts. RESULTS: Day 30 postimplant comparison of seed migration demonstrated a significant reduction in overall lung and pelvic seed migration from 25% (uncoated) to 4% (coated) (p < 0.0001). A measurable reduction in intraprostatic dose variability was observed in patients with the coated seeds when comparing 30 days dosimetry results for V100, V150, and D90 for prostate, and V110 for the rectum. A statistically significant reduction in the standard deviation from Day 0 to Day 30 for the above parameters for the prostate as well as for V110 of rectum was also observed. A significant improvement in implant quality at Day 30 was demonstrated using Radiation Therapy Oncology Group (RTOG) evaluation criteria range with the coated seeds cohort. CONCLUSIONS: PSI using coated seeds shows lower lung and pelvic seed migration compared with those using uncoated seeds and compares favorably to pelvic stranded seed migration reports. A higher concordance was observed with less dose variability in dosimetric parameters on Day 30 dosimetry compared with that on Day 0. Improvement in the implant quality was also observed using the RTOG criteria, suggesting reduced intraprostatic migration.

Frequency of severe valvular disease caused by mediastinal radiation among patients undergoing valve surgery in a community-based, regional academic medical center.

BACKGROUND: Our goal was to define the prevalence of radiation-induced valvular heart (RIVD) disease among patients undergoing cardiac valve surgery in a community-based, regional academic medical center. Mediastinal radiation is a treatment modality for various hematologic and solid malignancies; however, long-term cardiac complications, including radiation-induced valvular heart disease, can occur years after the radiation treatments. HYPOTHESIS: Mediastinal radiation exposure is an independent risk factor for valvular heart disease often necessitating valve replacement in patients without other risk factors for valve disease. METHODS: Between January 1, 1998 and September 1, 2007, we retrospectively analyzed our institution's cardiac surgical database over a 10 year period and identified 189 consecutive patients ≤ 50 years of age who underwent valve surgery. Using case-control matching, we assessed the prevalence of mediastinal radiation among these young patients with valve disease necessitating surgery and to their matched controls from all patients admitted to the hospital. RESULTS: Nine individuals (4.8%) were identified as having received previous mediastinal radiation, significantly increased from controls (p<0.0001), and 8 of whom had surgical or pathologic findings consistent with radiation damage. Compared with a matched case-control population, individuals who had severe valve disease and underwent valve replacement had a markedly increased prevalence of prior mediastinal radiation therapy. CONCLUSIONS: In conclusion, cardiologists must remain aware of the potential long term valvular complications in patients treated with mediastinal radiation. Increased surveillance for RIVD may be considered in the decades following radiation therapy.

An unusual presentation of invasive squamous cell carcinoma of the upper extremities in a patient with a history of severe electrical burns and chronic thermal and chemical exposure.

This is a case report that depicts an atypical presentation of very aggressive, metachronous invasive squamous cell carcinomas of the upper extremities in a patient with no prior history of precancerous or cancerous skin lesions and no significant solar radiation exposure. Potentially causative factors that played a role in the emergence of this aggressive form of skin cancer in this case study are multifactorial: (1) chronic thermal exposure of 3000 degrees F daily to his hands for an eight to ten-year time period; (2) chronic chemical exposure of DMSO solvent and higher levels of chemical contaminants such and finally; (3) a form of chronic immunosuppression as a result of his severe electrical burns that resulted in widespread second and third burns throughout his body.

Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation.

This study assessed the cumulative incidence of clinically significant cardiac disease in 1279 Hodgkin lymphoma patients treated with mediastinal irradiation and quantified the standard incidence ratios (SIRs) and absolute excess risks of cardiac procedures compared with a normal matched population. Cox regression analysis was used to explore factors associated with cardiac complications. Poisson regression analysis of SIRs was used to estimate the excess risk of cardiac interventions from mediastinal irradiation. After a median follow-up of 14.7 years, 187 patients experienced 636 cardiac events and 89 patients required a cardiac procedure. 5-, 10-, 15-, and 20-year cumulative incidence rates of cardiac events were 2.2%, 4.5%, 9.6%, and 16%. SIRs for cardiac procedures were increased for coronary artery bypass graft (3.19), percutaneous intervention (1.55), implantable cardioverter defibrillator or pacemaker placement (1.9), valve surgery (9.19), and pericardial surgery (12.91). Absolute excess risks were 18.2, 19.3, 9.4, 14.1, and 4.7 per 10 000 person-years, respectively. Older age at diagnosis and male sex were predictors for cardiac events. However, younger age at diagnosis was associated with excess risk specifically from radiation therapy compared with the general population. These results may help guideline development for both the types and timing of cardiac surveillance in survivors of Hodgkin lymphoma.

Partial vs. whole breast irradiation in a community hospital: a retrospective cohort analysis of 200 patients.

PURPOSE: We compared patients undergoing partial breast irradiation (PBI) with the MammoSite applicator (Cytyc Corp., Marlborough, MA) to a similar group of patients who underwent whole breast irradiation with external beam radiotherapy. METHODS AND MATERIALS: Stage 0-IIA breast cancer patients satisfying American Brachytherapy Society selection criteria and receiving accelerated PBI with the MammoSite system (n=100) were compared for toxicities with similarly staged patients receiving whole breast irradiation using tangential portals (n=100). The MammoSite applicator treatment was prescribed to a total dose of 34 Gy. External beam doses generally ranged from 60 to 66 Gy. RESULTS: Based on common toxicity criteria scores for acute toxicities, MammoSite patients experienced less cutaneous toxicity, fatigue, and breast pain and had higher Karnofsky performance status scores during the acute period than external beam patients but experienced more seroma pain during followup. These results were both statistically significant and clinically meaningful. CONCLUSIONS: In our institutional experience, PBI using the MammoSite applicator produces less acute toxicity than external beam radiotherapy of the whole breast but is associated with an increased incidence of seroma pain. The rate of disease recurrence in both cohorts was low.

The role of radiation therapy in the management of thyroid cancer.

The goal of this article is to review the various indications for the application of external beam radiotherapy in the management of thyroid cancer. This article includes a discussion of published literature to define risk variables that increase the risk of recurrence after surgery that might be mitigated by the use of radiation therapy. Clinical outcomes, recent technologic advances in treatment planning and radiation delivery, and potential morbidity associated with treatment are also reviewed.

Reduce in variation and improve efficiency of target volume delineation by a computer-assisted system using a deformable image registration approach.

PURPOSE: To determine whether a computer-assisted target volume delineation (CAT) system using a deformable image registration approach can reduce the variation of target delineation among physicians with different head and neck (HN) IMRT experiences and reduce the time spent on the contouring process. MATERIALS AND METHODS: We developed a deformable image registration method for mapping contours from a template case to a patient case with a similar tumor manifestation but different body configuration. Eight radiation oncologists with varying levels of clinical experience in HN IMRT performed target delineation on two HN cases, one with base-of-tongue (BOT) cancer and another with nasopharyngeal cancer (NPC), by first contouring from scratch and then by modifying the contours deformed by the CAT system. The gross target volumes were provided. Regions of interest for comparison included the clinical target volumes (CTVs) and normal organs. The volumetric and geometric variation of these regions of interest and the time spent on contouring were analyzed. RESULTS: We found that the variation in delineating CTVs from scratch among the physicians was significant, and that using the CAT system reduced volumetric variation and improved geometric consistency in both BOT and NPC cases. The average timesaving when using the CAT system was 26% to 29% for more experienced physicians and 38% to 47% for the less experienced ones. CONCLUSIONS: A computer-assisted target volume delineation approach, using a deformable image-registration method with template contours, was able to reduce the variation among physicians with different experiences in HN IMRT while saving contouring time.