Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer.

For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203-0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141-0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355-0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334-0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.

Severity of Financial Toxicity for Patients Receiving Palliative Radiation Therapy.

Introduction: Financial toxicity has negative implications for patient well-being and health outcomes. There is a gap in understanding financial toxicity for patients undergoing palliative radiotherapy (RT). Methods: A review of patients treated with palliative RT was conducted from January 2021 to December 2022. The FACIT-COST (COST) was measured (higher scores implying better financial well-being). Financial toxicity was graded according to previously suggested cutoffs: Grade 0 (score ≥26), Grade 1 (14-25), Grade 2 (1-13), and Grade 3 (0). FACIT-TS-G was used for treatment satisfaction, and EORTC QLQ-C30 was assessed for global health status and functional scales. Results: 53 patients were identified. Median COST was 25 (range 0-44), 49% had Grade 0 financial toxicity, 32% Grade 1, 15% Grade 2, and 4% Grade 3. Overall, cancer caused financial hardship among 45%. Higher COST was weakly associated with higher global health status/Quality of Life (QoL), physical functioning, role functioning, and cognitive functioning; moderately associated with higher social functioning; and strongly associated with improved emotional functioning. Higher income or Medicare or private coverage (rather than Medicaid) was associated with less financial toxicity, whereas an underrepresented minority background or a non-English language preference was associated with greater financial toxicity. A multivariate model found that higher area income (HR .80, P = .007) and higher cognitive functioning (HR .96, P = .01) were significantly associated with financial toxicity. Conclusions: Financial toxicity was seen in approximately half of patients receiving palliative RT. The highest risk groups were those with lower income and lower cognitive functioning. This study supports the measurement of financial toxicity by clinicians.

The Correlation Between Lymphocyte Nadir and Radiation Therapy for Soft Tissue Sarcoma: Defining Key Dosimetric Parameters and Outlining Clinical Significance.

Purpose: The objectives of this study were to identify key dosimetric parameters associated with postradiation therapy lymphopenia and uncover any effect on clinical outcomes. Methods and Materials: This was a retrospective review of 69 patients (between April 2010 and January 2023) who underwent radiation therapy (RT) as a part of curative intent for soft tissue sarcoma (STS) at a single academic institution. All patients with treatment plans available to review and measurable absolute lymphocyte count (ALC) nadir within a year after completion of RT were included. Results: Median follow-up was 22 months after the start of RT. A decrease in lymphocyte count was noted as early as during treatment and persisted at least 3 months after the completion of RT. On multivariable linear regression, the strongest correlations with ALC nadir were mean body dose, body V10 Gy, mean bone dose, bone V10 Gy, and bone V20 Gy. Five-year overall survival was 60% and 5-year disease-free survival was 44%. Advanced T-stage, chemotherapy use, use of intensity-modulated RT, lower ALC nadir, and the development of grade ≥2 lymphopenia at nadir were associated with worse overall survival and disease-free survival. Conclusions: Post-RT lymphopenia was associated with worse outcomes in STS. There were associations between higher body V10 Gy and bone V10 Gy and lower post-RT ALC nadir, despite the varying sites of STS presentation, which aligns with the well-known radiosensitivity of lymphocyte cell lines. These findings support efforts to reduce treatment-related hematopoietic toxicity as a way to improve oncologic outcomes. Additionally, this study supports the idea that the effect of radiation on lymphocyte progenitors in the bone marrow is more significant than that on circulating lymphocytes in treatments with limited involvement of the heart and lung.

Locoregional Treatment for Early-Stage Breast Cancer: Current Status and Future Perspectives.

BACKGROUND: The locoregional recurrence of breast cancer has been reduced due to the multidisciplinary approach of breast surgery, systemic therapy and radiation. Early detection and better surgical techniques contribute to an improvement in breast cancer outcomes. PURPOSE OF REVIEW: The purpose of this review is to have an overview and summary of the current evidence behind the current approaches to the locoregional treatment of breast cancer and to discuss its future direction. SUMMARY: With improved surgical techniques and the use of a more effective neoadjuvant systemic therapy, including checkpoint inhibitors and dual HER2-directed therapies that lead to a higher frequency of pathologic complete responses and advances in adjuvant radiation therapy, breast cancer patients are experiencing better locoregional control and reduced local and systemic recurrence. De-escalation in surgery has not only improved the quality of life in the majority of breast cancer patients, but also maintained the low risk of recurrence. There are ongoing clinical trials to optimize radiation therapy in breast cancer. More modern radiation technologies are evolving to improve the patient outcome and reduce radiation toxicities.

Effect of a same day appointment initiative on racial disparities in access for radiation oncology.

PURPOSE: We present our single-institution experience with the development of a same day access scheduling initiative for an outpatient radiation oncology unit, focusing on its potential influence on ameliorating racial disparities. METHODS AND MATERIALS: From March 2021 to August 2022, a pilot initiative was conducted such that all new patients referred to a tertiary care-based radiation oncology department were offered the ability to be seen as a same day consultation. The timespan of this analysis was categorized into 2 distinct successive periods over 36 months-a 18-month pre-initiative period (September 2019 to February 2021) and another subsequent one (March 2021 to August 2022). Descriptive statistics were used to study the impact of this initiative on access-related benchmarks. RESULTS: A total of 2897 patients were referred. Among the 2107 patients scheduled, three hundred and sixteen (15 %) opted for same day appointments. Black, Latino, and Asian patients were significantly more likely to use the same day access initiative versus Caucasian patients (p = 0.01). The same day access initiative increased the proportion of patients seen within 5 days from referral from 8 % to 34 % for Blacks, 12-57 % for Latinos, and 18-67 % for Asians, compared to 39-55 % for Caucasians (p < 0.001). The no-show rate was reduced from 20 % to 7 % and 14-5 %, for Black and Latino patients, respectively (p < 0.001). CONCLUSIONS: The implementation of a same day access initiative narrowed disparities with respect to access-related benchmarks.

The Axillary Lateral Vessel Thoracic Junction Is Not an Organ at Risk for Breast Cancer-Related Lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) is a treatment complication that significantly reduces patient quality of life. Regional nodal irradiation (RNI) may increase the risk of BCRL. Recently, a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) was identified as a potential organ at risk (OAR). Here, we set out to validate whether radiation dose to the ALTJ is associated with BCRL. METHODS AND MATERIALS: We identified patients with stage II-III breast cancer treated with adjuvant RNI from 2013 to 2018, excluding those with BCRL preradiation. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb >2.5 cm at any 1 encounter or ≥2 cm on ≥2 visits. All patients suspected of having BCRL at routine follow-up visits were referred to physical therapy for confirmation. The ALTJ was retrospectively contoured and dose metrics were collected. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. RESULTS: The study population included 378 patients with a median age of 53 years, median body mass index of 28.4 kg/m2, and median of 18 axillary nodes removed; 71% underwent mastectomy. Median follow-up was 70 months (interquartile range, 55-89.7 months). BCRL developed in 101 patients at a median of 18.9 months (interquartile range, 9.9-32.4 months), with a corresponding 5-year cumulative incidence BCRL of 25.8%. On multivariate analysis, none of the ALTJ metrics were associated with BCRL risk. Only increasing age, increasing body mass index, and increasing number of nodes were associated with a higher risk of developing BCRL. The 6-year locoregional recurrence rate was 3.2%, the axillary recurrence rate was 1.7%, and the isolated axillary recurrence rate was 0%. CONCLUSIONS: The ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL.

Utilization of cancer survivorship services during the COVID-19 pandemic in a tertiary referral center.

BACKGROUND: All Commission on Cancer-accredited comprehensive cancer centers offer survivorship programs (SPs) to women upon completion of treatment. These SPs can include clinical and non-clinical programming such as physical rehabilitation, emotional and psychosocial support, nutrition, and exercise programming. Concern about the availability and access to these programs during the COVID-19 pandemic has been described in recent literature. We sought to identify the impact of the COVID-19 pandemic on participation in these supportive services for breast cancer patients within a single institution. METHODS: The Ohio State University tertiary care center offers clinical and non-clinical breast cancer support services. Descriptive statistics were utilized to summarize referral and patient participation data from January 2019 through July 2021. Data from calendar year 2019 was used as a normative comparison for pre-COVID-19. In-person and telehealth use was tracked longitudinally. RESULTS: During the lockdown due to the COVID-19 pandemic (March through May 2020), provider referrals to SPs declined by 10%, while the overall total for the calendar year modestly increased from 1195 in 2019 to 1210 in 2020, representing a 1.3% increase. Psycho-oncology referrals increased from 280 to 318 (13.5%). The most significant change of participation rates in non-clinical SPs during the pandemic was utilization of exercise content, which increased by 220% from 2019 to 2020. The total proportion of breast cancer participants choosing an exercise program increased from 16.8% in 2019 to 42.2% in 2021, making it the most selected program area overall. Previously, nutrition was the most selected program area as it comprised 42.5% of overall utilization in 2019. CONCLUSION: The pandemic's potential to place barriers to participation in SPs is a legitimate concern. We found a modest decline in provider referrals to clinical services during the lockdown period, while patient-directed participation increased with more survivors engaging in exercise-based programs. Transitioning to virtual platforms served to maintain access for patients. IMPLICATIONS FOR CANCER SURVIVORS: As we grapple with the COVID-19 pandemic, patients with cancer deserve increased attention due to the expected stressors associated with the diagnosis. Those in the survivorship stage utilize services for psychosocial support, and the observed increase in utilization of SPs suggests an elevated need for connectivity. To meet this need, telehealth platforms have been expanded to allow for continued participation. It remains to be seen whether this will be sustained post-COVID-19 or whether reduced human contact will create new needs for programming.

Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

Stereotactic Radiosurgery for Women Older than 65 with Breast Cancer Brain Metastases.

BACKGROUND: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. METHODS: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan-Meier estimates and Cox proportional hazard regression method were used for survival analyses. RESULTS: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were <65 years old. Median age at RT was 72 years (range 65-84) compared to 52 years (31-64) in younger patients. There were significantly higher number of older women with ER/PR positive disease (75% vs. 49%, p = 0.036), while younger patients were more frequently triple negative (32% vs. 12%, p = 0.074) and HER2 positive (42% vs. 29%, p = 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%, p = 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%, p = 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months, p = 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months, p = 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70, p = 0.048), KPS ≤ 80 (HR = 2.24, p < 0.001), HER2 positive disease (HR = 0.46, p < 0.001), isolated CNS metastatic disease (HR = 0.29, p < 0.001), number of brain metastases treated with RT (HR = 1.06, p = 0.028), and fractionated SRS (HR = 0.53, p = 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32, p < 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06, p = 0.041), which implies a 6% additive risk of progression for every additional metastasis treated. CONCLUSIONS: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients.

Clinical outcomes of distal vaginal and vulvar cancer treated with image-guided brachytherapy.

PURPOSE: To evaluate treatment outcomes with image-guided brachytherapy (IGBT) for distal vaginal and vulvar cancers. MATERIAL AND METHODS: Women treated for distal vaginal or vulvar malignancies utilizing IGBT were retrospectively reviewed, and acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. RESULTS: Eighteen patients were included, out of which, twelve patients (66.7%) were with primary disease of the distal vagina and vulva, most commonly squamous cell carcinoma of the vulva (n = 8, 66.7%), and six with recurrent disease, most commonly recurrent endometrial carcinoma (n = 5, 83.3%). All patients received external beam radiation (EBRT) to a median dose of 45 Gy in 25 fractions, followed by IGBT (range of 15 to 27.5 Gy in 3 to 5 fractions). Mean follow-up was 20.6 months. Mean dose to high-risk clinical target volume (HR-CTV) D90 was 72.4 Gy. Mean D2cc for the rectum, bladder, and urethra were 50 Gy, 50.6 Gy, and 62.9 Gy, respectively. Five patients (27.8%) recurred. Three patients (16.7%) had local recurrence, 1 patient (5.6%) had distant recurrence only, and 1 patient (5.6%) had simultaneous regional and distant recurrence. Grade 3 acute toxicities included 1 (5.6%) vaginal stenosis, 6 (33.3%) dermatitis/mucositis, 2 (11.1%) vaginal pain, and 1 (5.6%) vaginal/vulvar infection. Grade 3 late toxicities comprised 3 (17.7%) cases of vaginal pain and 1 (5.9%) skin/vaginal necrosis. There were no grade 4 or higher toxicities. CONCLUSIONS: Definitive radiation therapy in the form of EBRT and IGBT provides meaningful loco-regional control in women with distal vaginal and vulvar cancers, with mainly skin and vaginal toxicity.

Toxicity and outcomes associated with high-dose rate brachytherapy for medically inoperable endometrial cancer.

PURPOSE: To evaluate toxicity in inoperable endometrial cancer (EC) treated with definitive radiation therapy (RT). MATERIALS AND METHODS: Patients treated with definitive RT for EC were retrospectively reviewed. EQD2 values were calculated for bladder, rectum, and sigmoid. Acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. RESULTS: Fifty-one patients were included. The majority of patients had endometrioid histology (N = 46, 90.2%) and Grade 1 disease (N = 32, 62.75%). Thirty-seven patients (72.5%) were treated with image-guided BT (IGBT) and 14 (27.5%) with two-dimensional BT. Forty patients (78.4%) received EBRT + BT and 11 (21.57%) received BT alone. No grade 2 (G2) or higher toxicities were reported with BT alone. G2 or higher acute toxicities with EBRT + BT were G2 proctitis (N = 2, 5.0%) and G3 proctitis (N = 1, 2.5%). Late toxicities included G3 vaginal stenosis (N = 1, 2.5%), proctitis (N = 1, 2.5%), enteritis (N = 1, 2.5%), and one G4 gastrointestinal bleed. One- and 2-year local control were 100% with BT alone and 93% and 89%, respectively, with EBRT + BT. One- and 2-year locoregional control were 100% with BT and 97% and 93%, respectively, with EBRT + BT. Recurrence-free survival was 89% at 1 and 2 years with BT alone compared to 87% and 80% with EBRT + BT. One- and 2-year overall survival were 88% and 72% with BT alone compared to 94% and 84% with EBRT + BT. There were no statistically significant differences in cancer control between the two groups. CONCLUSIONS: Women with inoperable EC treated with definitive RT have low toxicity rates and durable local control.

De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer.

In the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02-4.51, p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06-1.68, p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00-2.22, p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07-1.64, p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23-6.02, p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.

Analysis of Radiation Dose to the Shoulder by Treatment Technique and Correlation With Patient Reported Outcomes in Patients Receiving Regional Nodal Irradiation.

BACKGROUND/PURPOSE: Shoulder/arm morbidity is a late complication of breast cancer treatment with surgery and regional nodal irradiation (RNI). We set to analyze the impact of radiation technique [intensity modulated radiation therapy (IMRT) or 3D conformal radiation therapy (3DCRT)] on radiation dose to the shoulder with a hypothesis that IMRT use results in smaller volume of shoulder receiving radiation. We explored the relationship of treatment technique on long-term patient-reported outcomes using the quick disabilities of the arm, shoulder, and hand (q-DASH) questionnaire. MATERIALS/METHODS: We identified patients treated with adjuvant RNI (50 Gy/25 fractions) from 2013 to 2018. We retrospectively contoured the shoulder organ-at-risk (OAR) from 2 cm above the ipsilateral supraclavicular (SCL) planning target volume (PTV) to the inferior SCL PTV slice and calculated the absolute volume of shoulder OAR receiving 5-50 Gy (V5-V50). We identified patients that completed a q-DASH questionnaire ≥6 months from the end of RNI. RESULTS: We included 410 RNI patients: 54% stage III, 72% mastectomy, 35% treated with IMRT. IMRT resulted in significant reductions in the shoulder OAR volume receiving 20-50 Gy vs. 3DCRT. In total, 82 patients completed the q-DASH. The mean (SD) q-DASH=25.4 (19.1) and tended to be lower with IMRT vs. 3DCRT: 19.6 (16.4) vs. 27.8 (19.8), p=0.078. CONCLUSION: We found that IMRT reduces radiation dose to the shoulder and is associated with a trend toward reduced q-DASH scores ≥6 months post-RNI in a subset of our cohort. These results support prospective evaluation of IMRT as a technique to reduce shoulder morbidity in breast cancer patients receiving RNI.

Dosimetric parameters associated with radiation-induced esophagitis in breast cancer patients undergoing regional nodal irradiation.

BACKGROUND/PURPOSE: Rates of acute esophagitis in breast cancer patients undergoing regional nodal irradiation (RNI) are under-reported. We set to identify esophageal dose-volume constraints associated with grade 2 esophagitis (G2E). We hypothesized that the G2E rate was higher with intensity modulated radiation therapy (IMRT) vs. 3D conformal radiation therapy (3DCRT). MATERIALS/METHODS: We identified patients that received RNI (50 Gy/25 fractions) from 1/2013 to 6/2019. We retrospectively contoured the esophagus in a consistent manner and recorded esophageal mean dose, max dose, and V10-V50. Our primary endpoint was the G2E rate. Receiver operating characteristics curves analysis (e.g., Youden's J statistic) were used to determine the cutpoints for the dosimetric parameters which were then tested in logistic regression models. RESULTS: We identified 531 patients (50% left-sided; 41% IMRT; 16.2% G2E). G2E was significantly higher in IMRT vs. 3DCRT patients (23.6% vs. 10.9%, p < 0.0001). All esophageal dosimetric parameters were significantly associated with G2E after adjusting for age and laterality. The cutpoints for esophageal mean dose, V10 and V20 were 11 Gy, 30%, and 15%, respectively. The associations between the dichotomized dose-volume parameters and G2E were OR = 3.82 (95% CI 2.28-6.40, p < 0.0001) for esophageal mean dose, OR = 5.37 (95% CI 3.01-9.58, p < 0.0001) for esophageal V10, and OR = 3.23 (95% CI 1.93-5.41, p < 0.0001) for esophageal V20. CONCLUSION: In patients receiving RNI with modern techniques, we found that G2E occurs in >15%, and more frequently with IMRT. These data strongly support the routine contouring of the esophagus in RNI planning, and our constraints should be incorporated in future prospective protocols of RNI.

Thyroid-optimized and thyroid-sparing radiotherapy in oral cavity and oropharyngeal carcinoma: A dosimetric study.

BACKGROUND: Radiation-induced hypothyroidism is a common toxicity of head and neck radiation. Our re-planning study aimed to reduce thyroid dose while maintaining target coverage with IMRT. METHODS: We retrospectively identified patients with oral-cavity (n = 5) and oropharyngeal cancer (n = 5). Treatment plans were re-optimized with 45 Gy thyroid mean dose constraint, then we cropped the thyroid out of PTVs and further reduced thyroid dose. Target coverage was delivering 100% dose to ≥ 93% of PTV and 95% of dose to > 99% of PTV. RESULTS: Originally, average mean dose to thyroid was 5580 cGy. In model I, this dropped to 4325 cGy (p < 0.0001). In model II, average mean dose was reduced to 3154 cGy (p < 0.0001). For PTV low and PTV int, all had acceptable target coverage. CONCLUSION: In patients with oral-cavity and oropharyngeal cancers, mean dose could be significantly reduced using a thyroid-optimized or thyroid-sparing IMRT technique with adequate coverage.

Clinical Effectiveness of an Adaptive Treatment Planning Algorithm for Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Node-Positive Breast Cancer Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy.

PURPOSE: Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node-positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns. METHODS AND MATERIALS: Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post). RESULTS: Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post). CONCLUSIONS: An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints.

A series of typical and atypical cases of Bazex syndrome: Identifying the red herring to avoid delaying cancer treatment.

Bazex syndrome is a rare paraneoplastic dermatosis that precedes diagnosis of cancer. Awareness of this syndrome is important, as it allows early detection of underlying malignancy and may prevent misdiagnosis and delays in cancer treatment.

Primary vs nodal site PET/CT response as a prognostic marker in oropharyngeal squamous cell carcinoma treated with intensity-modulated radiation therapy.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) in staging of advanced oropharyngeal squamous cell carcinoma (OPSCC) and at 3 months posttreatment (PETpost) is often utilized to assess response. The significance of lymph node vs primary site treatment response is incompletely understood. METHODS: We reviewed 230 patients treated with radiation therapy. PETpost response was graded at primary and nodal sites and correlated with survival. RESULTS: Median age was 58, and 83% were p16-positive. Median follow-up was 24.3 months. Nodal response at PETpost predicted improved 2-year local recurrence-free survival (LRFS) (93% vs 72%, P =.004), 2-year disease-free survival (DFS) (80% vs 61.3%, P =.021), and 2-year overall survival (OS) (89% vs 83%, P =.051), while primary response only predicted improved 2-year LRFS (91% vs 76% P = .035). CONCLUSION: In OPSCC patients, both nodal and primary response at 3 months on PET/CT predicted for improved LRFS, but only nodal response predicted DFS and OS.

Cell cycle actions of parathyroid hormone-related protein in non-small cell lung carcinoma.

Parathyroid hormone-related protein (PTHrP), a paraneoplastic protein expressed by two-thirds of human non-small cell lung cancers, has been reported to slow progression of lung carcinomas in mouse models and to lengthen survival of patients with lung cancer. This study investigated the effects of ectopic expression of PTHrP on proliferation and cell cycle progression of two human lung adenocarcinoma cell lines that are normally PTHrP negative. Stable transfection with PTHrP decreased H1944 cell DNA synthesis, measured by thymidine incorporation, bromodeoxyuridine uptake, and MTT proliferation assay. A substantial fraction of PTHrP-positive cells was arrested in or slowly progressing through G1. Cyclin D2 and cyclin A2 protein levels were 60-70% lower in PTHrP-expressing cells compared with control cells (P < 0.05, N = 3 independent clones per group), while expression of p27(Kip1), a cyclin-dependent kinase inhibitor, was increased by 35 +/- 9% (mean +/- SE, P < 0.05) in the presence of PTHrP. Expression of other cyclins, including cyclins D1 and D3, and cyclin-dependent kinases was unaffected by PTHrP. PTHrP did not alter the phosphorylation state of Rb, but decreased cyclin-dependent kinase (CDK) 2-cyclin A2 complex formation. Ectopic expression of PTHrP stimulated ERK phosphorylation. In MV522 cells, PTHrP had similar effects on DNA synthesis, cyclin A2 expression, pRb levels, CDK2-cyclin A2 association, and ERK activation. In summary, PTHrP appears to slow progression of lung cancer cells into S phase, possibly by decreasing activation of CDK2. Slower cancer cell proliferation could contribute to slower tumor progression and increased survival of patients with PTHrP-positive lung cancer.