Photobiomodulation During Chemoradiation for Head and Neck Cancer: Effect on Mucositis, Weight Loss, and Feeding Tube Dependence.

Purpose: The standard therapeutic approach in head and neck cancer (HNC) involves multimodality therapy, including surgery, radiation therapy (RT), or chemoradiation therapy (CRT). Treatment complications (mucositis, weight loss, and feeding tube dependence [FTD]) can result in treatment delays, incomplete treatment, and decreased quality of life. Studies on photobiomodulation (PBM) have shown promising reductions in mucositis severity but with little quantitative supporting data. We compared complications for patients with HNC receiving PBM with those in patients who did not, hypothesizing that PBM improves mucositis severity, weight loss, and FTD. Methods and Materials: Medical records of 44 patients with HNC treated with CRT or RT from 2015 to 2021 were reviewed (22 PBM, 22 controls; median age, 63.5 years; range, 45-83 years). Between-group outcomes of interest included maximum mucositis grade, weight loss, and FTD 100 days after initiation of treatment. Results: Median RT doses were 60 Gy (PBM) and 66 Gy (control). Eleven patients treated with PBM received CRT; 11 received RT alone (median of 22 PBM sessions [range, 6-32]). Sixteen control group patients received CRT; 6 received RT alone. Median maximal mucositis grades were 1 in the PBM group and 3 in the control group (P < .0001). The adjusted odds of higher mucositis grade were only 0.024% (P < .0001; 95% confidence interval, 0.004-0.135) in PBM compared with the control group. Conclusions: PBM may have a role in decreasing complications related to RT and CRT for HNC, mainly mucositis severity.

Management of the parotid for high-risk cutaneous squamous cell carcinoma: A review from the salivary section of the American Head and Neck Society.

BACKGROUND: Metastases to the parotid nodal basin in patients with high-risk cutaneous squamous cell carcinoma (HRcSCC) impact disease specific survival (DSS) and overall survival (OS). METHODS: A writing group convened by the Salivary Section of the American Head and Neck Society (AHNS) developed contemporary, evidence-based recommendations regarding management of the parotid nodal basin in HRcSCC based on available literature, expert consultation, and collective experience. The statements and recommendations were then submitted and approved by the AHNS Salivary Committee. RESULTS: These recommendations were developed given the wide variation of practitioners who treat HRcSCC in order to streamline management of the parotid nodal basin including indications for imaging, surgery, radiation, and systemic treatment options as well. CONCLUSIONS: This clinical update represents contemporary optimal management of the parotid nodal basin in HRcSCC and is endorsed by the Salivary Section of the AHNS.

Telemedicine for Cranial Radiosurgery Patients in a Rural U.S. Population: Patterns and Predictors of Patient Utilization.

Introduction: Telemedicine retains potential for increasing access to specialty providers in underserved and rural communities. COVID-19 accelerated adoption of telehealth beyond rural populations, serving as a primary modality of patient-provider encounters for many nonemergent diagnoses. Methods: From 2020 to 2021, telemedicine was incorporated in management of stereotactic radiosurgery patients. Retrospective data on diagnoses, demographics, distance to primary clinic, and encounter type were captured and statistically analyzed using descriptive measures and Cox proportional regression modeling. Graphical representation of service areas was created using geo-mapping software. Results: Patients (n = 208) completed 331 telemedicine encounters over 12 months. Metastases and meningiomas comprised 60% of diagnoses. Median age was 62 years with median household income and residential population of $44,752 and 7,634 people. The one-way mean and median travel distances were 74.6 and 66.3 miles. The total potential road mileage for all patients was 44,596 miles. A total of 118 (57%) patients completed video visits during the first encounter, whereas 90 (43%) opted for telephone encounters. At 12 months, 138 patients (66%) utilized video visits and 70 (34%) used telephone visits. Predictors of video visit use were video-enabled visit during the first encounter (hazard ratio [HR] 2.806, p < 0.001), total potential distance traveled (HR 1.681, p < 0.05), and the need for more than one visit per year (HR 2.903, p < 0.001). Discussion: Telemedicine can be effective in radiosurgery practice with predictors of video-enabled use being pre-existing patient comfort levels with videoconferencing, total annual travel distance, and number of visits per year. Age, rural population status, and household income did not impact telemedicine use in our patient cohort.

Stereotactic radiosurgery for glioblastoma considering tumor genetic profiles: an international multicenter study.

OBJECTIVE: Molecular profiles, such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) methylation status, have important prognostic roles for glioblastoma patients. The authors studied the efficacy and safety of stereotactic radiosurgery (SRS) for glioblastoma patients with consideration of molecular tumor profiles. METHODS: For this retrospective observational multiinstitutional study, the authors pooled consecutive patients who were treated using SRS for glioblastoma at eight institutions participating in the International Radiosurgery Research Foundation. They evaluated predictors of overall and progression-free survival with consideration of IDH mutation and MGMT methylation status. RESULTS: Ninety-six patients (median age 56 years) underwent SRS (median dose 15 Gy and median treatment volume 5.53 cm3) at 147 tumor sites (range 1 to 7). The majority of patients underwent prior fractionated radiation therapy (92%) and temozolomide chemotherapy (98%). Most patients were treated at recurrence (85%), and boost SRS was used for 12% of patients. The majority of patients harbored IDH wild-type (82%) and MGMT-methylated (62%) tumors. Molecular data were unavailable for 33 patients. Median survival durations after SRS were similar between patients harboring IDH wild-type tumors and those with IDH mutant tumors (9.0 months vs 11 months, respectively), as well as between those with MGMT-methylated tumors and those with MGMT-unmethylated tumors (9.8 vs. 9.0 months, respectively). Prescription dose > 15 Gy (OR 0.367, 95% CI 0.190-0.709, p = 0.003) and treatment volume > 5 cm3 (OR 1.036, 95% CI 1.007-1.065, p = 0.014) predicted overall survival after controlling for age and IDH status. Treatment volume > 5 cm3 (OR 2.215, 95% CI 1.159-4.234, p = 0.02) and absence of gross-total resection (OR 0.403, 95% CI 0.208-0.781, p = 0.007) were associated with inferior local control of SRS-treated lesions in multivariate models. Nine patients experienced adverse radiation events after SRS, and 7 patients developed radiation necrosis at 59 to 395 days after SRS. CONCLUSIONS: Post-SRS survival was similar as a function of IDH mutation and MGMT promoter methylation status, suggesting that molecular profiles of glioblastoma should be considered when selecting candidates for SRS. SRS prescription dose > 15 Gy and treatment volume ≤ 5 cm3 were associated with longer survival, independent of age and IDH status. Prior gross-total resection and smaller treatment volume were associated with superior local control.

Stereotactic radiosurgery for IDH wild type glioblastoma: an international, multicenter study.

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutation status is recommended used for diagnosis and prognostication of glioblastoma patients. We studied efficacy and safety of stereotactic radiosurgery (SRS) for patients with recurrent IDH-wt glioblastoma. METHODS: Consecutive patients treated with SRS for IDH-wt glioblastoma were pooled for this retrospective observational international multi-institutional study from institutions participating in the International Radiosurgery Research Foundation. RESULTS: Sixty patients (median age 61 years) underwent SRS (median dose 15 Gy and median treatment volume: 7.01 cm3) for IDH-wt glioblastoma. All patients had histories of surgery and chemotherapy with temozolomide, and 98% underwent fractionated radiation therapy. MGMT status was available for 42 patients, of which half of patients had MGMT mutant glioblastomas. During median post-SRS imaging follow-up of 6 months, 52% of patients experienced tumor progression. Median post-SRS progression free survival was 4 months. SRS prescription dose of > 14 Gy predicted longer progression free survival [HR 0.357 95% (0.164-0.777) p = 0.009]. Fifty-percent of patients died during post-SRS clinical follow-up that ranged from 1 to 33 months. SRS treatment volume of > 5 cc emerged as an independent predictor of shorter post-SRS overall survival [HR 2.802 95% CI (1.219-6.444) p = 0.02]. Adverse radiation events (ARE) suggestive of radiation necrosis were diagnosed in 6/55 (10%) patients and were managed conservatively in the majority of patients. CONCLUSIONS: SRS prescription dose of > 14 Gy is associated with longer progression free survival while tumor volume of > 5 cc is associated with shorter overall survival after SRS for IDH-wt glioblastomas. AREs are rare and are typically managed conservatively.

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies.

PURPOSE: Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls. METHODS AND MATERIALS: Meta-analysis of Observational Studies in Epidemiology guidelines were used to perform a comprehensive search identifying case-control or randomized studies reporting RT toxicity outcomes for patients with CVD versus controls. Data were synthesized from studies reporting grade 2 to 3 or more (G2/3 +) acute and late RT toxicities. Results were analyzed with fixed effects meta-analysis on the random-effects model for between-study heterogeneity; otherwise, the fixed-effects model was used. Hazard ratio or odds ratio (OR) were the effect-size estimators, as appropriate. RESULTS: Ten studies were included, with 4028 patients (CVD: 406, control: 3622). Patients with CVD had higher rates of acute G2/3 + toxicity (26.2% vs 16.5%, OR [odds ratio] 2.01; P < .001) and late G2/3 + toxicity (18.4% vs 10.1%, OR 2.37; P < .001). Higher rates of late G2/3 + toxicity were observed for CVD patients with systemic lupus erythematous (21% vs 9.7%; OR 2.55, P = .03), systemic scleroderma (31.8% vs 9.7%, OR 3.85; P = .03), rheumatoid arthritis (11.7% vs 8.4%, OR = 2.56; P = .008), and those irradiated to the pelvis/abdomen (32.2% vs 11.9%, OR 3.29; P = .001), breast (14.7% vs 4.4%, OR 3.51; P = .003), thorax (12.5% vs 8.7%, OR 3.46; P < .001), and skin (14.6% vs 5.2%, OR 2.59; P = .02). Late grade 5 toxicities were significantly higher for patients with CVD, although absolute rates were low (3.9% vs 0.6%, OR = 7.81; P = .01). CONCLUSIONS: Moderate and severe toxicities are more likely in patients with CVD, with variable risk depending on toxicity grade, CVD subtype, treatment site, and dose. Severe toxicities are uncommon. These factors should be considered when informing patients of treatment-related risks and monitoring for morbid treatment sequelae.

Dose homogeneity analysis of adjuvant radiation treatment in surgically resected brain metastases: Comparison of IORT, SRS, and IMRT indices.

PURPOSE: Although surgery remains a treatment option for symptomatic brain metastases, the need for adjuvant radiation after surgery is widely accepted as standard. Despite a multitude of randomized trials aimed at identifying the ideal radiation treatment plan for surgically resected metastases, the development of new delivery regiments necessitates a periodic re-evaluation of dosimetric performance/outcome. Here, we compare the homogeneity index (HI) across three platforms: single-session stereotactic radiosurgery (SRS), multisession stereotactic radiotherapy, and intraoperative radiotherapy (IORT). METHODS AND MATERIALS: Patients treated with IORT after surgical resection of brain metastases were identified and dosimetric parameters collected from the dose-volume histograms based on the development of conformal plans for adjuvant radiation using Gamma Knife-SRS (GK-SRS), linear accelerator based intensity-modulated radiation therapy, and IORT. HIs were calculated using four established methods and compared across platforms within the patient cohort. Statistical analyses were performed using analysis of variance. RESULTS: The mean maximal doses for the GK-SRS and IMRT plans were 30 Gy and 29 Gy with margin prescription doses of 16 Gy and 24 Gy, respectively. The IORT dose was 30 Gy to the applicator surface. HIs varied based on calculation methods, but maintained consistency when comparing across platforms with IORT having the lower mean HI value (0.56; 95% confidence interval (CI) 0.55-0.60) in single-fraction treatment, compared with GK-SRS (0.77; 95% CI 0.76-0.80). The mean multisession IMRT HI was lower than both single-fraction treatment modalities at 0.41 (95% CI 0.40-0.42). CONCLUSIONS: When using the HI as the primary dosimetric parameter for adjuvant radiation plans after surgical resection of brain metastases IORT offers improved dose homogeneity compared with GK-SRS in single-fraction treatment, whereas fractionated LINAC-based IMRT was superior with respect to the HI in comparison among all three methods.

Clinicopathologic Features and Radiation Therapy Utilization in Patients with Male Breast Cancer: A National Cancer Database Study.

Male breast cancer (MBC) accounts for approximately 1% of all breast cancers, limiting the data characterizing clinicopathologic features and treatment outcomes in patients with MBC. This paucity of data has led to most of our treatment guidance being extrapolated from patients with female breast cancer (FBC). From 1998 to 2012, data were captured using the National Cancer Database to identify patients with nonmetastatic MBC (n = 23 305) and FBC (n = 2 678 061). Tumor and clinicopathologic features were obtained and compared. Patients with MBC were more likely to have invasive disease, T2-4 tumors, centrally located tumors, positive lymph nodes, estrogen receptor-positive or progesterone receptor-positive tumors, lymphovascular space invasion, and were less likely to have Her2/neu-positive or triple-negative tumors. All of these differences were statistically significant (P < .001). Treatment comparisons showed that patients with MBC were more likely to undergo mastectomy and less likely to undergo breast-conserving surgery with postoperative radiation utilization found to be less in patients with MBC, both as part of breast-conserving therapy (BCT) and for postmastectomy radiation treatment (PMRT) (P < .001). Stage-by-stage comparisons showed that median survival, 5-year, and 10-year overall survival (OS) rates are lower in patients with MBC vs patients with FBC (P < .001). The utilization of adjuvant radiation, both BCT and PMRT, was shown to improve 5- and 10-year OS (P < .001). Male breast cancer clinicopathologic features appear to be unfavorable in relation to FBC and adjuvant radiation is shown beneficial in survival outcomes. Further investigation is needed to help guide future utilization and treatment with radiation, systemic, and endocrine manipulation in this small population of patients with MBC.

Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma.

OBJECTIVE: To correlate microscopic margin status with survival and local control in a large cohort of patients from a high-volume pancreatic cancer center. DESIGN: Retrospective database review. A uniform procedure for margin analysis was used with 4-color inking (neck, portal vein groove, uncinate, and posterior pancreatic margin) by the surgeon in the operating room. SETTING: A tertiary care hospital. PATIENTS: We reviewed patients who underwent pancreaticoduodenectomy between September 1, 1997, and December 31, 2008, from a prospective, institutional database. MAIN OUTCOME MEASURES: Using Cox regression models, we identified pathologic characteristics associated with local recurrence (LR) after controlling for potential confounding variables. Overall and LR-free survival curves were generated by the Kaplan-Meier method. RESULTS: Of 285 patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma, 97 (34.0%) had 1 or more positive microscopic margins (uncinate, 16.5%; portal vein groove, 8.8%; neck, 7.7%; and posterior, 10.5%). A total of 198 patients (69.5%) recurred, with the first site of failure being LR only in 47 (23.7%), local plus distant recurrence in 42 (21.2%), and distant recurrence only in 109 (55.1%). Patients with LR only were significantly more likely to have lymph node involvement (adjusted hazard ratio, 2.66; 95% CI, 1.25-5.63) or a positive posterior margin (adjusted hazard ratio, 4.27; 95% CI, 2.07-8.81). Patients with a positive posterior margin had significantly poorer LR-free survival with (P < .001) or without (P = .01) lymph node involvement. CONCLUSIONS: When systematically assessed, the incidence of positive microscopic margins is high. Positive posterior margins and lymph node involvement were each independently and significantly associated with LR.

Induction of Th17 cells in the tumor microenvironment improves survival in a murine model of pancreatic cancer.

An important mechanism by which pancreatic cancer avoids antitumor immunity is by recruiting regulatory T cells (Tregs) to the tumor microenvironment. Recent studies suggest that suppressor Tregs and effector Th17 cells share a common lineage and differentiate based on the presence of certain cytokines in the microenvironment. Because IL-6 in the presence of TGF-ß has been shown to inhibit Treg development and induce Th17 cells, we hypothesized that altering the tumor cytokine environment could induce Th17 and reverse tumor-associated immune suppression. Pan02 murine pancreatic tumor cells that secrete TGF-ß were transduced with the gene encoding IL-6. C57BL/6 mice were injected s.c. with wild-type (WT), empty vector (EV), or IL-6-transduced Pan02 cells (IL-6 Pan02) to investigate the impact of IL-6 secretion in the tumor microenvironment. Mice bearing IL-6 Pan02 tumors demonstrated significant delay in tumor growth and better overall median survival compared with mice bearing WT or EV Pan02 tumors. Immunohistochemical analysis demonstrated an increase in Th17 cells (CD4(+)IL-23R(+) cells and CD4(+)IL-17(+) cells) in tumors of the IL-6 Pan02 group compared with WT or EV Pan02 tumors. The upregulation of IL-17-secreting CD4(+) tumor-infiltrating lymphocytes was substantiated at the cellular level by flow cytometry and ELISPOT assay and mRNA level for retinoic acid-related orphan receptor γt and IL-23R by RT-PCR. Thus, the addition of IL-6 to the tumor microenvironment skews the balance toward Th17 cells in a murine model of pancreatic cancer. The delayed tumor growth and improved survival suggests that induction of Th17 in the tumor microenvironment produces an antitumor effect.