Search

Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent radiation therapy. Regression rates and derived model parameters correlated significantly with clinical outcome (P < 0.001; median follow-up: 6.2 years). The 6-year local tumor control rate was 87% versus 54% using radiosensitivity (2-Gy surviving fraction S2 < 0.70 vs. S2 ≥ 0.70) as a predictor (P = 0.001) and 89% vs. 57% using dead-cell resolving time (T1/2 < 22 days versus T1/2 ≥ 22 days, P < 0.001). The 6-year disease-specific survival was 73% versus 41% with S2 < 0.70 versus S2 ≥ 0.70 (P = 0.025), and 87% vs. 52% with T1/2 < 22 days versus T1/2 ≥ 22 days (P = 0.002). Our approach illustrates the promise of volume-based tumor response modeling to improve early outcome predictions that can be used to enable personalized adaptive therapy. Cancer Res; 70(2); 463–70

Free Article from Predicting Outcomes in Cervical Cancer: A Kinetic Model of Tumor Regression during Radiation Therapy

The standard of care for elderly or frail patients with glioblastoma (GBM) is 40 Gy in 15 fractions of radiotherapy. However, this regimen has a lower biological effective dose (BED) compared with the Stupp regimen of 60 Gy in 30 fractions. It is hypothesized that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) is safe and efficacious.Elderly or frail patients with GBM treated with 52.5 Gy in 15 fractions were pooled from 3 phase 1/2 studies and a prospective observational study. Overall survival (OS) and progression-free survival (PFS) were defined time elapsing between surgery/biopsy and death from any cause or progression of disease.Sixty-two newly diagnosed patients were eligible for this pooled analysis of individual patient data. The majority (66%) had a Karnofsky performance status (KPS) score70. The median age was 73 years. The median OS and PFS were 10.3 and 6.9 months, respectively. Patients with KPS scores ≥70 and70 had a median OS of 15.3 and 9.5 months, respectively. Concurrent chemotherapy was an independent prognostic factor for improved PFS and OS. Grade 3 neurologic toxicity was seen in 2 patients (3.2%). There was no grade 4/5 toxicity.This is the only analysis of elderly/frail patients with GBM prospectively treated with a hypofractionated radiation regimen that is isoeffective to the Stupp regimen. Treatment was well tolerated and demonstrated excellent OS and PFS compared with historical studies. This regimen gives the elderly/frail population an alternative to regimens with a lower BED. Randomized trials are needed to validate these results.

Background: The response rates to immune checkpoint inhibitors (ICI) remain low (13-20%) in metastatic head and neck cancer patients and better understanding of factors predictive of response to these agents is urgently needed. Here we explore the impact of smoking status, marijuana use and alcohol on treatment outcomes in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with ICI. Methods: We performed a retrospective analysis of 201 R/M HNSCC patients treated with ICI between January 15th 2016 and April 9th 2020 at a single institution. Results: Gender: 154 male (77%), 47 female (23%). Median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), nivolumab+ipilimumab 10 (5%). Line of therapy: first: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), larynx 26 (13%), other sites 46 (23%). p16 tumor status: negative 132 (66%), positive 69 (34%). Smoking status: former 111 (55%), never 54 (27%), current 36 (18%), median pack-year 18 (IQR: 0-37). Alcohol use: yes 110 (55%), no 91 (54%). Marijuana use: yes 47 (23%), no 154 (77%). Overall response rate: 36 (18%). Median OS: 12 months (95% CI: 9.4-14.8). Tobacco: former (HR: 0.75, 95% CI: 0.50, 1.11), current (HR: 0.58, 95% CI: 0.33, 1.02). Marijuana: yes (HR: 0.93, 95% CI: 0.58, 1.49). Alcohol: yes (HR: 1.04, 95% CI: 0.72, 1.49). Conclusion: In our cohort, smoking status, marijuana use and alcohol consumption did not have a statistically significant impact on OS in patients with R/M HNSCC treated with ICI. Trial registration: retrospectively registered.

Background Gamma knife (GK) and linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) both offer excellent local control in the management of multiple brain metastases. The efficacy and toxicity of LINAC and GK SRS have not been directly compared in the modern era. We studied outcomes in patients treated with LINAC SRS and GK at two separate institutions. Methods We identified patients treated with either LINAC or GK who were treated to ≥2 lesions and had available follow up. LINAC patients were treated using single-isocenter multitarget technique. We used Cox regression, Fine and Gray competing risks regression, and nearest neighbor propensity score matching to account for confounders and imbalance between cohorts. Kaplan–Meier curves were used to estimate overall survival and rates of radionecrosis. Results We identified 391 patients who were treated in 537 courses to a total 2699 lesions (LINAC: 1014, GK: 1685). After propensity score matching, GK was associated with similar overall survival (HR = 0.86; 95% CI 0.59–1.24; p = 0.41) and higher rate of radionecrosis (HR = 3.83; 95% CI 1.66–8.84; p = 0.002) compared to LINAC. In a secondary propensity score matched analysis comparing radionecrosis in single-fraction LINAC and GK, GK remained associated with higher incidence of radionecrosis (HR = 4.42; 95% CI 1.28–15.29; p = 0.019). Conclusions In this multi-institutional study, we found similar overall survival with lower incidence of radionecrosis in patients treated with LINAC compared to GK SRS. These findings are hypothesis generating and should be validated in an independent cohort.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The “Summary of the Guidelines Updates” section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.

Purpose/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiation response. Our study analyzed the HNSCC tumor samples from The Cancer Genome Atlas (TCGA) to investigate the relationship between different HNSCC tumor subsites, hypoxia, and local tumor microbiome composition. Results: A total of 357 patients were included [Oral cavity (OC) = 226, Oropharynx (OPx) = 53, and Larynx/Hypopharynx (LHPx) = 78], of which 12.8%, 71.7%, and 10.3%, respectively, were HPV positive. The mean (SD) hypoxia scores were 30.18 (11.10), 24.31 (14.13), and 29.53 (12.61) in OC, OPx, and LHPx tumors, respectively, with higher values indicating greater hypoxia. The hypoxia score was significantly higher for OC tumors compared to OPx (p = 0.044) and LHPx (p = 0.002). There was no significant correlation between hypoxia and HPV status. Pseudomonas sp. in OC, Actinomyces sp. and Sulfurimonas sp. in OPx, and Filifactor, Pseudomonas and Actinomyces sp. in LHPx had the strongest association with the hypoxia score. Materials/Methods: Tumor RNAseq samples from TCGA were processed, and the R package “tmesig” was used to calculate gene expression signature, including the Buffa hypoxia (BH) score, a validated hypoxia signature using 52 hypoxia-regulated genes. Microbe relative abundances were modeled with primary tumor location and a high vs. low tertile BH score applying a gamma-distributed generalized linear regression using the “stats” package in R, with adjusted p-value < 0.05 considered significant. Conclusions: In our study, oral cavity tumors were found to be more hypoxic compared to other head and neck subsites, which could potentially contribute to their radiation resistance. For each subsite, distinct microbial populations were over-represented in hypoxic tumors in a subsite-specific manner. Further studies focusing on an association between microbiome, hypoxia, and patient outcomes are warranted.

Retrospective studies have suggested that older adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have better survival rates when treated using a pediatric ALL regimen administered by pediatric treatment teams. To address the feasibility and efficacy of using a pediatric treatment regimen for AYA patients with newly diagnosed ALL administered by adult treatment teams, we performed a prospective study, CALGB 10403, with doses and schedule identical to those in the Children’s Oncology Group study AALL0232. From 2007 to 2012, 318 patients were enrolled; 295 were eligible and evaluable for response. Median age was 24 years (range, 17-39 years). Use of the pediatric regimen was safe; overall treatment-related mortality was 3%, and there were only 2 postremission deaths. Median event-free survival (EFS) was 78.1 months (95% confidence interval [CI], 41.8 to not reached), more than double the historical control of 30 months (95% CI, 22-38 months); 3-year EFS was 59% (95% CI, 54%-65%). Median overall survival (OS) was not reached. Estimated 3-year OS was 73% (95% CI, 68%-78%). Pretreatment risk factors associated with worse treatment outcomes included obesity and presence of the Philadelphia-like gene expression signature. Use of a pediatric regimen for AYAs with ALL up to age 40 years was feasible and effective, resulting in improved survival rates compared with historical controls. CALGB 10403 can be considered a new treatment standard upon which to build for improving survival for AYAs with ALL. This trial was registered at www.clinicaltrials.gov as #NCT00558519.

Background To report our institutional experience with intraoperative radiotherapy for persistent or recurrent head and neck cancer. Methods Sixty-one patients were treated with salvage surgery and intraoperative radiation therapy (IORT). Fifty-eight patients (95%) had previously received external beam radiotherapy (EBRT) as a component of their definitive therapy. Forty-four patients (72%) had squamous cell carcinoma (SCC). Surgical margins were positive in 28 patients (46%). IORT was prescribed to a median dose of 12.5 Gy (range, 10-17.5). Twenty-three patients (38%) received a course of postoperative EBRT (median 45 Gy). Clinical outcomes were retrospectively reviewed and univariate analysis was performed using log-rank tests to correlate clinical outcomes with histology, surgical margin, and adjuvant therapy. Results Median follow-up among surviving patients was 15.9 months. Median progression-free survival (PFS) and overall survival (OS) were 9.8 and 19.1 months, respectively. One- and 2-year rates of locoregional control (LRC) were 59% and 35%, respectively. One- and 2-year rates of PFS were 39% and 19%, respectively. One- and 2-year rates of OS were 62% and 42%, respectively. Overall survival was better for non-SCC histology (P = .03). For SCC patients, negative surgical margin showed a trend toward improved PFS (P = .09) and OS (P = .06). There was one grade-5 toxicity due to carotid rupture. Conclusions IORT has shown effective LRC and OS with an acceptably low rate of severe toxicity at our institution. OS was significantly better for non-SCC histology. For SCC patients, there is a trend toward improved PFS and OS associated with negative surgical margins.

PURPOSE The standard of care (SOC) for elderly or frail glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy. However, this regimen has a lower BED compared to the Stupp regimen, 60 Gy in 30 fractions. We hypothesize that isoeffective hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to standard of care. METHODS Elderly GBM patients treated with 52.5 Gy in 15 fractions were pooled from 2 phase II studies, 1 phase 1 and a prospective observation study. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Univariate and multivariate analyses were performed. RESULTS 62 newly-diagnosed patients were eligible for this analysis. Median follow-up was 10 months. The median OS and PFS was 10.3 and 6.9 mos, respectively. Patients with KPS ≥ 70 and < 70 had a median OS of 15.3 and 9.5 mos. No survival difference was seen between unmethylated and methylated patients with a median OS of 10.2 and 10.3 months, respectively. Multivariable analysis demonstrated that concurrent chemotherapy was an independent prognostic factor for improved PFS and OS. Grade 3 neurologic toxicity was seen in 2 patients (3.2%). CONCLUSION This is the first pooled, prospective analysis of elderly/frail GBM patients treated with dose-escalated hypofractionated radiation. Treatment was well tolerated and demonstrated excellent OS and PFS, exceeding that from prior elderly trials (Roa; 6.5 mo [poor KPS]/Perry; 9.3mo [good KPS]). This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. Future prospective trials are needed to validate these results.

Purpose/Objective(s) Radiotherapy (RT) is a cornerstone modality in treating head and neck cancers in the primary and salvage settings. Maximum tolerated dose to the brachial plexus and other factors contributing to brachial plexus injury in the re-irradiation setting are poorly understood. To define radiation dose and other clinical factors associated with the brachial plexus injury in patients treated with re-irradiation for recurrent head and neck cancers. Materials/Methods We analyzed 47 brachial plexus re-irradiation between 2015 and 2020. A first course of radiation for head and neck cancer, developed recurrent disease, and then underwent salvage re-irradiation. DICOM plans and contours for all patients were reviewed by two authors and via a prospective multidisciplinary chart rounds. Common terminology criteria for adverse events (CTCAE) was used to define the brachial plexus injury after the second course of radiation. We used ROC curves to evaluate the cutoff values. Kaplan-Meier and logistic regression were used to test the correlation between the variables and the outcome. Results Median prescription dose from the 1st course was 70 Gy (range: 60-70) and from the 2nd course was 66 Gy (46-70) in 2 Gy per fraction. All patients received photon volumetric modulated arc therapy; 74% received concurrent chemotherapy (CRT) during the 1st course (Cisplatin 30%, Carboplatin +/- Paclitaxel 23% and Cetuximab 21%), 74% received CRT during the 2nd course (Carboplatin/Paclitaxel 40%, Cetuximab 17%, Cisplatin 13% and Nivolumab 4%) and 53% received CRT twice. The median time interval between the two RT courses was 24 months (range, 8-221 months). The median cumulative maximum dose (Dmax) to brachial plexus was 97 Gy (range, 64-144 Gy). At a median follow-up of 9 months (range, 1-47 months), the cumulative incidence of brachial plexopathy (CIBPP) was 17% at 1 year. This consisted of two cases with pain alone, one case with numbness alone, two cases with weakness alone and one case with combination of pain and numbness. The median time to development of symptoms was 8.2 months (range, 1-15 months). Among patients with a Dmax greater than vs less than 106 Gy, the 1-year cumulative incidence of BPP was 42% vs 4% P = 0.005. V80 > 1cc (1-yr CIBPP 34% vs 4% P = 0.03) and V90 > 0.3cc (32% vs 4%, P = 0.046) associated with increased risk of BPP. The use of concurrent cisplatin during re-irradiation was associated with increased risk of BPP (OR 39 CI 4.263-356.81, P = 0.001). Other variables like gender, history of neck surgery, use of other kind of systemic therapy, use of cisplatin during the first course of RT, mean cumulative dose, V60, V70, V100 and the interval between the first and the second courses of radiation were not associated with increased risk of BPP. The 1-year OS was 78% and the 1-year PFS was 52%. Conclusion Cumulative incidence of radiation-induced BPP after re-irradiation was 17% at 1 year. Dmax > 106 Gy, higher V80/V90, and the use of concurrent cisplatin during re-irradiation, were associated with increased risk of BPP.

PURPOSE/OBJECTIVE(S) The standard of care for elderly glioblastoma patients (GBM) is 40 Gy in 15 fractions with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that dose escalated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions. MATERIALS/METHODS Elderly patients (> 60 yo) who received hypofractionated radiation with TMZ were included in this analysis. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared with pairwise tests. Univariate and multivariate analyses were performed. RESULTS 66 newly-diagnosed patients were eligible for this analysis. 39 patients were treated with 40 Gy in 15 fractions, and 27 patients were treated with 52.5 Gy in 15 fractions. The median follow up for this cohort was 8.8 months. Patients were well balanced with no significant differences in age, sex, MGMT, extent of resection, or KPS. The median OS was 7.9 months in the 40 Gy arm and 13.1 months in the 52.5 Gy arm (P = 0.035). For unmethylated patients, the median OS was 6.7 months in the 40 Gy arm and 11.3 months in the 52.5 Gy arm (P = 0.012). Increasing planning treatment volume (P = 0.007) was associated with decreased OS. On multivariate analysis, MGMT methylation (HR 0.45 [0.23-0.87] P = 0.018) and dose escalation (HR 0.45 [0.21-0.96] 0.04) remained independent prognostic factors for OS. In a multivariate model for PFS, only dose-escalation was significant (HR 0.49 [0.25-0.98] P = 0.045). No significant differences in toxicity were observed between treatment groups. CONCLUSION Dose-escalation to 52.5 Gy in 15 fractions was associated with superior OS and PFS compared to standard of care 40 Gy in 15 fractions. This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. These hypothesis generating data support dose-escalated hypofractionation in future prospective trials. AUTHOR DISCLOSURE H.K. Perlow: None. M. Yang: None. B. Klamer: None. R. Raval: None. D.M. Blakaj: None. A.L. Arnett: None. S. Beyer: None. J.C. Grecula: None. M. Ammirati: None. J.B. Elder: None. R.R. Lonser: None. D. Hardesty: None. S.S. Ong: None. P. Giglio: None. C. Pillainayagam: None. J. Goranovich: None. A. Chakravarti: None. V. Gondi: Partner; Radiation Oncology Consultants, Ltd. Honoraria; UpToDate, RaySearch. Partnership; Radiation Oncology Consultants, Ltd. Co-Principal Investigator; NRG Oncology. P.D. Brown: None. J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.

Purpose/Objective(s) Radiation treatment planning for meningioma conventionally involves MRI contrast enhanced images to define residual tumor. However, the gross tumor volume may be difficult to delineate for patients with a meningioma in the skull base, sagittal sinus, or post resection. Advanced PET imaging using 68(GA)DOTATATE PET, which has been shown to be more sensitive and specific than MRI imaging, can be used for target volume delineation in these circumstances. We hypothesize that 68(GA)DOTATATE PET scan-based treatment planning will lead to differences in radiation treatment volumes and will be more precise compared to standard MRI alone. Materials/Methods Our study evaluated retrospective, deidentified, and blinded gross tumor volume (GTV) contour delineation of 5 CNS specialists (3 neuroradiologists, 2 CNS radiation oncologists) for 26 patients diagnosed with a meningioma who received both a 68(GA)DOTATATE PET and an MRI for radiation treatment planning. Both the MRI and the PET-based GTV were non-sequentially contoured by each physician for each patient. We defined a significant difference in volume delineation if there was > 100% difference in contoured volume found for 80% of physicians or more when comparing MRI and PET. A PET only lesion was defined as any lesion not seen on MRI but delineated on PET imaging by at least 80% of physicians. This lesion would need to be non-adjacent to the MRI based contours for the same patient. Results The mean volume of MRI based contours was 12.5 ccs (range 0.55-62 ccs). The mean volume for PET directed contours was 13.7 ccs (range 0.24-94 ccs). We found 15/26 (58%) patients had at least a 100% difference in volume between PET and MRI for 80% of physician contours. 8/26 (31%) patients had new non-adjacent areas contoured on PET that were not contoured by these physicians on the corresponding MRI. These new areas would not have been in the traditional MRI based volumes. Conclusion We found a significant difference in PET based volumes with 58% showing major differences in volume and 31% showing new areas not seen on MRI. This has major implications on tumor control. Our study supports that 68(GA)DOTATATE PET imaging can help radiation oncologist be more precise with radiation treatment volumes. Utilization of 68(GA)DOTATATE PET may find undetected areas of disease which in turn can improve local control and progression free survival. 68(GA)DOTATATE PET guided treatment planning should be studied prospectively.

Objectives: Neutrophil-lymphocyte ratio (NLR) has been associated with mortality in non-small cell lung cancer (NSCLC), but its association with recurrence in locally advanced NSCLC (LA-NSCLC), specifically, is less established. We hypothesized pre- and post-treatment NLR would be associated with recurrence and mortality. Methods: We studied the association of pre-treatment NLR (pre-NLR) and post-treatment NLR at 1 (post-NLR1) and 3 months (post-NLR3) with outcomes in patients with LA-NSCLC treated with chemoradiation. Pre-NLR was dichotomized by 5, an a priori cutoff previously shown to be prognostic in LA-NSCLC. Post-NLR1 and post-NLR3 were dichotomized by their medians. Linear and logistic regression were used to correlate thoracic vertebral body dose with post-NLR. Results: We identified 135 patients treated with chemoradiation for LA-NSCLC between 2007 and 2016. Median follow-up for living patients was 61.1 months. On multivariable analysis, pre-NLR ≥ 5 was associated with worse overall survival (HR = 1.82; 95% CI 1.15 – 2.88; p = 0.011), but not with any recurrence, locoregional recurrence, or distant recurrence. Post-NLR1 ≥ 6.3 was not associated with recurrence or survival. Post-NLR3 ≥ 6.6 was associated with worse overall survival (HR = 3.27; 95% CI 2.01– 5.31; p < 0.001), any recurrence (HR = 2.50; 95% CI 1.53 – 4.08; p < 0.001), locoregional recurrence (HR = 2.50; 95% CI 1.40 – 4.46; p = 0.002), and distant recurrence (HR = 2.53; 95% CI 1.49 – 4.30; p < 0.001). Post-NLR3 ≥ 6.6 correlated with thoracic vertebral body volume receiving 5 Gy (p = 0.026), 10 Gy (p = 0.041), and 60 Gy (p = 0.044). Conclusion: Pre-treatment NLR is associated with worse overall survival and post-treatment NLR is associated with worse survival and recurrence. Additionally, post-treatment NLR at 3 months correlates with thoracic vertebral body dose. These findings should be validated independently and prospectively studied.

Background Spine surgery is indicated for select patients with mechanical instability, pain, and/or malignant epidural spinal cord compression, with or without neurological compromise. Stereotactic body radiotherapy (SBRT) is an option for durable local control (LC) for metastatic spine disease. Objective To determine factors associated with LC and progression-free survival (PFS) for patients receiving postoperative stereotactic spine radiosurgery. Methods We analyzed consecutive patients from 2013 to 2019 treated with surgical intervention followed by SBRT. Surgical interventions included laminectomy and vertebrectomy. SBRT included patients treated with 1 to 5 fractions of radiosurgery. We analyzed LC, PFS, overall survival (OS), and toxicity. Univariate and multivariate analyses were performed. Results A total of 63 patients were treated with a median follow-up of 12.5 mo. Approximately 75% of patients underwent vertebrectomy and 25% underwent laminectomy. One-year cumulative incidence of local failure was 19%. LC was significantly improved for patients receiving radiosurgery ≤40 d from surgery compared to that for patients receiving radiosurgery ≥40 d from surgery, 94% vs 75%, respectively, at 1 yr (P = .03). Patients who received preoperative embolization had improved LC with 1-yr LC of 88% vs 76% for those who did not receive preoperative embolization (P = .037). Significant predictors for LC on multivariate analysis were time from surgery to radiosurgery, higher radiotherapy dose, and preoperative embolization. The 1-yr PFS and OS was 56% and 60%, respectively. Conclusion Postoperative radiosurgery has excellent and durable LC for spine metastasis. An important consideration when planning postoperative radiosurgery is minimizing delay from surgery to radiosurgery. Preoperative embolization and higher radiotherapy dose were associated with improved LC warranting further study.

The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on "Signs and Symptoms of SCLC" and "Principles of Pathologic Review."

A negative interim positron emission tomography/computerized tomography (PET/CT) after 1 to 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with newly diagnosed, nonbulky stage I or II Hodgkin lymphoma (HL) predicts a low relapse rate. This phase 2 trial was designed to determine if a population of patients with early-stage disease can be treated with short-course ABVD without radiation therapy (RT) on the basis of a negative interim PET/CT, thereby limiting the risks of treatment. Between 15 May 2010 and 21 February 2013, 164 previously untreated patients with nonbulky stage I/II HL were enrolled, and 149 were included in the final analysis. Patients received 2 cycles of ABVD followed by PET. Deauville scores 1 to 3 were negative (≤ liver uptake) based on central review. PET − patients received 2 more cycles of ABVD, and PET + patients received 2 cycles of dose-intense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus 3060-cGy involved-field RT. The primary objective was to determine 3-year progression-free survival (PFS) for the PET − group. One hundred thirty-five patients (91%) were interim PET − , and 14 patients (9%) were PET + . With median follow-up time of 3.8 years, the estimated 3-year PFS was 91% for the PET − group and 66% for the PET + group (hazard ratio, 3.84; 95% confidence interval, 1.50-9.84; P = .011). There was 1 death as a result of suicide. Four cycles of ABVD resulted in durable remissions for a majority of patients with early-stage nonbulky HL and a negative interim PET. This trial was registered at www.clinicaltrials.gov as #NCT01132807.

OBJECTIVES: to examine the impact of radiotherapy center volume on overall survival in patients with oral cavity and oropharyngeal squamous cell carcinoma getting adjuvant radiation therapy after receiving surgery at a high-volume center. MATERIALS AND METHODS: a retrospective study was conducted on patients with oral cavity squamous cell carcinoma or oropharyngeal squamous cell carcinoma treated surgically at a tertiary institution from 2000 to 2012 who received adjuvant radiotherapy. The outcome variable was overall survival and the independent variable was location of adjuvant radiation therapy: high-volume center (HVC) versus low-volume center (LVC). Cox proportional hazards models were used to assess associations between predictors of death. Variables that were found to be significant at the α = 0.10 were included in a multivariable model. RESULTS: 336 patients met inclusion criteria. One-hundred thirty-nine patients received adjuvant radiation therapy at HVC and 197 patients received adjuvant radiation therapy at LVC. A univariate Cox proportional hazards model identified the variables location, age, marital status, subsite, T stage, extracapsular extension, and smoking status to include in a multivariable model. Age, subsite, T stage, and extracapsular extension were independent predictors of overall survival (p < .05). Location (p=.55), marital status (p=.29), and smoking status (p=.22) were not statistically significant predictors of survival. CONCLUSION: After surgery at a HVC, the volume of adjuvant radiation therapy center was not significantly associated with overall survival. Significant predictors of survival included age, subsite, T stage, and extracapsular extension.

Introduction Elderly patients account for the majority of lung cancer diagnoses but are poorly represented in clinical trials. We evaluated the overall survival (OS) of elderly patients with stage III NSCLC treated with definitive radiation compared with that of patients treated with definitive chemoradiation. Methods We conducted a comparative effectiveness study of radiation therapy versus chemoradiation in elderly (≥70 years old) patients with stage III NSCLC not treated surgically diagnosed from 2003 to 2014; the patients were identified by using the National Cancer Database. Two cohorts were evaluated: patients (n = 5023) treated with definitive radiation (≥59.4 Gy) and patients (n = 18,206) treated with definitive chemoradiation. Chemoradiation was further defined as concurrent (radiation and chemotherapy started within 30 days of each other) or sequential (radiation started >30 days after chemotherapy). We compared OS between the treatment groups by using the Kaplan-Meier method and Cox proportional hazards regression before and after propensity score matching (PSM). Results Treatment with chemoradiation was associated with improved OS versus that with radiation both before PSM (hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.64-0.68, p Conclusions We found that definitive chemoradiation resulted in a survival advantage compared with definitive radiation in elderly patients. Sequential chemotherapy and radiation was superior to concurrent chemoradiation. Although prospective trials are needed, this analysis suggests that chemoradiation should be strongly considered for elderly patients and the optimal sequencing of chemotherapy and radiation remains an unanswered question for this patient population.

PURPOSE: To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer. METHODS AND MATERIALS: Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V(5)-V(60)) were retrospectively recorded. Logistic regression was used to test associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability was evaluated using the Lyman-Kutcher-Burman (LKB) model for HT3+, and receiver operating characteristics analysis was used to determine dosimetric cut-points. RESULTS: We identified 201 patients, the majority having NSCLC (n = 162, 81%) and stage III to IV disease (n = 179, 89%). All patients received either cisplatin/etoposide (n = 107, 53%) or carboplatin/paclitaxel (n = 94, 47%). Median RT dose was 60 Gy (range, 60–70 Gy). The rate of HT3+ was 49% (n = 99). Increasing mean TVB dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.041, 95% confidence interval 1.004–1.080, P = .032), as were increasing TVB V(5) to V(20).These dosimetric correlates to HT3+ persisted on multivariate analysis. Constrained optimization of the LKB model for HT3+ yielded the parameters: n = 1, m = 1.79, and TD(50) = 21.4 Gy. Optimal cut-points identified were V(5) = 65%, V(10) = 60%, V(20) = 50%, and mean dose = 23.5 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+. CONCLUSIONS: We found that mean TVB dose and low-dose parameters (V(5)-V(20)) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n = 1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.

Introduction Kilovoltge cone beam computed tomography (kV-CBCT) allows for tumor localization and response assessment during definitive chemoradiotherapy for locally advanced NSCLC. We hypothesize that significant tumor volume loss occurs early during radiotherapy and that the extent of volume loss correlates with clinical outcomes. Methods A total of 52 patients with locally advanced NSCLC treated with definitive chemoradiotherapy were reviewed. kV-CBCT images were used to contour primary gross tumor volumes at four time points during treatment. Patients were dichotomized according to absolute and relative volume changes at each time point. Statistical analyses were performed to evaluate correlations between volume changes and clinical outcomes. Results The median gross tumor volumes were 77.1, 48.3, 42.5, and 29.9 cm3 for fractions 1, 11, 21, and final, respectively. Greater relative volume loss between fractions 1 and 21 correlated with improved distant control (hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.13–0.94, p = 0.038) and overall survival (HR = 0.40, 95% CI: 0.16–0.98, p = 0.046). Greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.17–0.88, p = 0.02) and trended toward improved overall survival (HR = 0.43, 95% CI: 0.17–1.06, p = 0.07). On multivariate analysis, greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.16–0.97, p = 0.041) and overall survival (HR = 0.31, 95% CI: 0.11–0.88, p = 0.027). Conclusions Significant primary tumor volume loss occurs early during radiotherapy for locally advanced NSCLC. Greater relative tumor volume loss during treatment correlates with improved disease control and overall survival. Thus, kV-CBCT has potential to be used as a practical prognostic imaging marker.

PURPOSE Radiation treatment planning for meningiomas conventionally involves MRI contrast enhanced images to define residual tumor. However, the gross tumor volume may be difficult to delineate for patients with a meningioma in the skull base, sagittal sinus, or post resection. Advanced PET imaging using 68(GA)DOTATATE PET, which has been shown to be more sensitive and specific than MRI imaging, can be used for target volume delineation in these circumstances. We hypothesize that 68(GA)DOTATATE PET scan-based treatment planning will lead to smaller radiation volumes and will detect additional areas of disease compared to standard MRI alone. METHODS Our data evaluated retrospective, deidentified, and blinded gross tumor volume (GTV) contour delineation with 7 CNS specialists (3 neuroradiologists, 4 CNS radiation oncologists) for 26 patients diagnosed with a meningioma who received both a 68(GA)DOTATATE PET and an MRI for radiation treatment planning. Both the MRI and the PET were non-sequentially contoured by each physician for each patient. RESULTS The mean MRI volume for each physician ranged from 24.14-35.52 ccs. The mean PET volume for each physician ranged from 10.59-20.54 ccs. The PET volumes were significantly smaller for 6 out of the 7 physicians. In addition, 7/26 (27%) patients had new non-adjacent areas contoured on PET by at least 6 of the 7 physicians that were not contoured by these physicians on the corresponding MRI. These new areas would not have been in the traditional MRI based volumes. CONCLUSION Our study supports that 68(GA)DOTATATE PET imaging can help radiation oncologist create smaller and more precise radiation treatment volumes. Utilization of 68(GA)DOTATATE PET may find undetected areas of disease which in turn can improve local control and progression free survival. 68(GA)DOTATATE PET guided treatment planning should be studied prospectively.

PURPOSE/OBJECTIVE(S) The standard of care (SOC) for elderly or frail glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy. However, this regimen has a lower BED compared to the Stupp regimen, 60 Gy in 30 fractions. We hypothesize that dose escalated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to standard of care. MATERIALS/METHODS Elderly GBM patients treated with 52.5 Gy in 15 fractions were pooled from 2 phase II studies, 1 phase 1 and a prospective observation study. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Univariate and multivariate analyses were performed. RESULTS Sixty-two newly diagnosed patients were eligible for this analysis. Median follow-up was 10 months. The median OS and PFS was 10.3 and 6.7 months, respectively. Patients with KPS ≥ 70 and < 70 had a median OS of 15.3 and 9.5 months. No survival difference was seen between unmethylated and methylated patients with a median OS of 10.2 and 10.3 months, respectively. Univariate analysis demonstrated younger age (P = 0.018) and concurrent chemo (P < 0.001) were associated with improved OS and gross total resection (P = 0.010), smaller PTV volume (P = 0.008) and concurrent chemo (P = 0.015) associated with improved PFS. Multivariate analysis demonstrated concurrent chemo to be an independent prognostic factor. Grade 3 or higher neurologic toxicity was seen in 2 patients (3.2%). CONCLUSION This is the first pooled, prospective analysis of elderly/frail GBM patients treated with dose-escalated hypofractionated radiation. Treatment was well tolerated and demonstrated excellent OS and PFS, exceeding that from prior elderly trials (Roa; 6.5 months [poor KPS]/Perry; 9.3 months [good KPS]). This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. Future prospective trials are needed to validate these results.

PURPOSE/OBJECTIVE(S) Circumferential spine stereotactic body radiotherapy (CsSBRT) is indicated in selected patients with circumferential vertebral bone/epidural spine metastatic disease. There is a paucity of data on the feasibility, toxicity and outcomes of CsSBRT. This study aimed to determine the feasibility, toxicities and outcomes of CsSBRT treatments. MATERIALS/METHODS We analyzed sixty-four circumferential treatments from 2013-2019 treated with SBRT in the post-operative and intact spine metastatic setting. Radiotherapy was delivered with 1-5 fractions. We analyzed the local control, side effects and the dose-volume histogram for each treatment. RESULTS In the sixty-four plans, the median follow-up was 15 months (1-63 months). All images and treatment plans were reviewed by the CNS radiation oncology and neuro-radiology. The most common regimen used was 27 Gy in 3 fractions. The 12-month cumulative incidence of local failure was 15%. In this cohort, there was eight local failures; 5 of them had recurrence in the epidural space, two had disease progression in the vertebral body and one had disease progression in the vertebral body with extension to the right lateral compartment. The planning target volume (PTV) coverage was ≥95% in 60 plans (94%). The median biologically effective dose (BED) for delivered dose, mean dose, minimum dose and D95% were 51.3 Gy, 54.13 Gy, 29.3 Gy and 51.3 Gy, respectively. The median BED max dose to spinal cord and cauda equine were 59 Gy (15-114) and 68 Gy (7.5-136). There were no grade 3 or higher early or late toxicities reported. CONCLUSION In this retrospective analysis of patients who received CsSBRT treatments, we were able to achieve excellent local control safely with minimal toxicity. We recommend at least 2-4 mm space between the target and the spinal cord or cauda equine in order to deliver CsSBRT. AUTHOR DISCLOSURE K. Dibs: None. J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.A. Olausson: None. E. Bourekas: None. D. Boulter: None. A.S. Ayan: None. E.R. Cochran: None. V. Yildiz: None. J.C. Grecula: None. A.L. Arnett: None. R. Raval: None. S. Beyer: None. T. Scharschmidt: None. J.B. Elder: None. A. Chakravarti: None. E. Mendel: None. D.M. Blakaj: None.

Background The purpose of this study was to review long-term outcomes of sinonasal adenoid cystic carcinoma (ACC) and to clarify its association with human papillomavirus (HPV). Methods The medical records of 23 patients with sinonasal ACC treated with primary surgical resection between 1998 and 2013 were reviewed. Tissue specimens were available for 17 patients. The p16 testing was performed using immunohistochemistry (IHC), and HPV infection was determined using quantitative polymerase chain reaction (PCR) with primers targeting the E6/E7 region. Results Two of the 17 samples showed strong and diffuse p16 staining, whereas the remaining 15 cases showed p16-positivity isolated to the luminal cells. Only one of the p16-positive cases was positive for HPV. The 5-year local failure, disease-free survival (DFS), and overall survival (OS) were 51%, 52%, and 62%, respectively. Conclusion Local failures are common with advanced sinonasal ACC, and the association of HPV with true sinonasal ACC is low.

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.

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.

6038 Background: Immune checkpoint inhibitors (ICI) are currently approved in the treatment of patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The majority of pts will progress on ICI. Little is known regarding the best treatment approach for this patient population. We previously showed that the combination of weekly carboplatin, paclitaxel and cetuximab was associated with reduced risk of grade 3/4 toxicities, which makes it an ideal regimen in this setting. Here; we report the outcomes of pts with R/M HNSCC who were treated with chemotherapy alone vs weekly chemotherapy plus cetuximab after progression on ICI. Methods: Between January 15th 2016 and April 9th 2020, 154 pts who progressed on ICI were analyzed. Among these pts, 64 had received subsequent systemic therapy and met the inclusion criteria. Progression Free Survival (PFS) was defined as the time elapsed between initiation of subsequent chemotherapy and tumor progression or death. Overall Survival (OS) was defined as the time elapsed between initiation of subsequent chemotherapy to death. Descriptive statistics and Cox regression were used to explore study variables. Results: 64 pts received subsequent chemotherapy after progression on ICI. 28 pts (44%) received a combination of weekly chemotherapy plus cetuximab. This regimen included carboplatin AUC 1.5, paclitaxel 45 mg/m2, and cetuximab loading dose of 400mg/m2 followed by weekly dose of 250 mg/m2. 36 pts (56%) received chemotherapy alone without cetuximab. These regimens included capecitabine, afatinib, and gemcitabine, among others. Sex: 51 males (80%), 13 females (20%), age (median): 61 (IQR: 53-66), tumor site: oropharynx 32 (50%), oral cavity 11 (17%), larynx 8 (12%), other sites 13 (21%). P16 status: negative 36 (56%), positive 28 (44%). Prior ICI drug: pembrolizumab 34 (53%), nivolumab 26 (41%), ipilimumab + nivolumab 4 (6%). Median follow up: 9 months (IQR: 5-13). Overall response rate: weekly chemotherapy plus cetuximab 32%, chemotherapy alone 22% (p = 0.4). Pts who received chemotherapy alone had a median PFS of 3.2 months (CI: 2-5) vs 5.6 months (CI: 4.3-10.1) in the weekly chemotherapy plus cetuximab group. After adjusting for p16 status and prior ICI drug, PFS was improved in the group that received weekly chemotherapy plus cetuximab vs. chemotherapy alone (HR: 0.52; CI: 0.28-0.98; p = 0.042). Median OS was 10 months (CI: 8.5-NR) in the weekly chemotherapy plus cetuximab group vs 8.7 months (CI: 5.7-13.8) in the chemotherapy alone group (HR: 0.84; CI: 0.4-1.8; p = 0.8). Conclusions: Pts with R/M HNSCC who progressed on ICI experience longer PFS with the addition of cetuximab to weekly chemotherapy. Further investigation in a larger cohort of pts is needed to fully assess the impact on survival for this treatment combination.

6030 Background: Immune checkpoint inhibitors (ICI) therapy is approved for patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The majority of pts will die within two years of diagnosis. We have shown that pretreatment clinical characteristics may predict overall survival (OS). Here, we expand our analysis to a total of 201 pts. Methods: Between January 15,2016 and April 9, 2020, 201 pts with R/M HNSCC were treated with ICI as first, second line and beyond. Data on p16 status, hemoglobin (Hb), albumin, lactate dehydrogenase (LDH), neutrophil, platelet and lymphocyte count was recorded initially. OS was defined from the start of ICI to death. Progression Free Survival (PFS) was defined from the start of ICI to disease progression (PD) or death. A nomogram was created using the rms package to generate individualized survival prediction. Results: 201 pts were analyzed, sex: 154 male (77%), 47 female (23%), median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), ipilimumab+nivolumab 10 (5%). Line of therapy: First: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), others 72 (36%). p16 status: negative 132 (66%), positive 69 (34%). Laboratory values: Median neutrophil count: 4.58 (IQR: 3.43-6.47), Median lymphocyte count: 0.69 (IQR: 0.47-1.08), Median Platelet count: 229 (IQR: 187-300), hemoglobin (Hb) normal/low 101/100 (50%/50%), albumin: normal/low 156/45 (78%/22%), LDH: normal/high 124/77 (62%/38%). Overall response rate: 36 (18%). Median OS: 12 months (CI: 9.4-14.8), median PFS: 4 months (CI: 3.5-5.7). The variables associated with OS were neutrophil count (high) [HR 1.28 (1.08 – 1.51), p=0.004], lymphocyte count (high) [HR 0.75 (0.60 – 0.95), p=0.015], albumin (low) [HR 2.06 (1.37 – 3.10), prd and 66th percentile. Median OS in the good risk group was 24 months (CI: 18.5-NR), average risk group 13.8 months (CI: 11-20), poor risk group 2.3 months (CI: 1.7-4.4). The discrimination of the model after internal validation was c-index of 0.72. Conclusions: A small percentage of R/M HNSCC pts treated with ICI have good long-term survival outcomes. In a larger cohort, we internally validated the utilization of a simple, inexpensive and widely accessible nomogram based on clinical and laboratory variables which can predict OS in this patient population.

During radiotherapy to the head and neck, metallic dental restorations produce secondary electrons that increase dose to nearby tissue causing painful ulcers that contribute to morbidity during treatment and lead to breaks in therapy. Various protective measures have been tested with simplified phantoms and beam arrangements. Our objective was to quantitatively assess electron scatter using an anatomical phantom and modern beam configurations. A tissue-equivalent phantom was created to simulate the oral cavity with gold crowns on opposing molars. Four-millimeter ethylene copolymer dosimetric dental stents were produced. The phantom was placed in a water bath to simulate soft tissue. Radiation was delivered in opposed lateral, nine-field intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) configurations. A GafChromic EBT3 film was used to simulate the mucosal surfaces of the tongue and the buccal mucosa. The film readings were then converted to isodose plots using DoseLab. With opposed beams, a 32 % reduction in maximum dose was measured in the occlusal plane with the use of stents. In the nine-field IMRT and VMAT plans, maximum dose to the adjacent film was reduced by approximately 40 % with the use of the dental stent. This approximately 40 % dose reduction implies that patients’ oral mucosae adjacent to dental fixtures could receive more than 100 Gy during a course of definitive radiotherapy to the head and neck without dental stents. In this era of increasing IMRT/VMAT utilization, our results emphasize the value of stent use to improve morbidity and reduce treatment breaks for patients undergoing head and neck radiotherapy.

BACKGROUND: Gene Mediated Cytotoxic Immunotherapy (GMCI) generates a polyvalent anti-tumor immune response through local delivery of aglatimagene besadenovec (AdV-tk) which synergizes with standard of care (SOC). METHODS: A Phase II trial was designed to evaluate overall survival (OS) after GMCI + SOC compared to a concurrent matched control group meeting protocol criteria and SOC at an institution not active in the treatment trial. Primary efficacy analysis was planned on the null hypothesis of no improvement in the 2-yr survival over the SOC group with planned subset analysis of significant disease prognostic factors. RESULTS: From 2006 to 2010, 48 patients completed SOC + GMCI and 134 SOC in the matched cohort. There were no dose-limiting toxicities. Fever, fatigue and headache were the most common GMCI-related symptoms. Median OS was 17.1 and 13.5 months for GMCI + SOC and SOC, respectively (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.52-0.99, p = 0.0417). Median PFS was 8.1 and 6.5 months for GMCI + SOC and SOC, respectively (HR 0.66, 95% CI 0.48-0.91, p = 0.0100). OS at 1- 2- and 3-years increased from 57%, 22% and 8% to 67%, 35% and 19%, respectively. The improvement was mostly in patients that underwent gross total resection: median OS increased from 16.9 to 25 months (p = 0.0492); 1- 2- and 3-year survival rates from 64%, 28% and 6% to 90%, 53% and 32%. CONCLUSIONS: GMCI can be safely combined with SOC in newly diagnosed malignant gliomas. Survival rates compared favorably to historical reports and a matched control group. Survival outcomes were significantly improved in patients with minimal residual disease after total resection. The 2-yr survival rate met the planned statistical threshold for significance. This is the first study to demonstrate a correlation between maximum debulking and a survival advantage using immunotherapy. These data strongly support further evaluation of GMCI for malignant gliomas.

Trans-oral robotic surgery (TORS) has emerged as an important surgical treatment option in the management of human papillomavirus (HPV)-positive and -negative oropharynx cancer. However, treatment selection is paramount to ensure that patients will not require multimodality adjuvant therapy. In this study, we determined predictors of adjuvant therapy in TORS-treated patients. The National Cancer Database (NCDB) was used to identify patients with newly diagnosed clinical T1-T4, N0-N3 oropharyngeal squamous cell carcinoma who underwent TORS between 2010&ndash, 2016. Kaplan&ndash, Meier survival analysis was used to estimate overall survival (OS). A total of 2999 patients were studied, and the five-year OS for the entire cohort was 82.5%, and for HPV-positive and -negative cohorts it was 88.3% and 67.9%, respectively (p &lt, 0.001). Among all patients treated with TORS, 35.1% of patients received no additional treatment, 33.5% received adjuvant radiation alone (RT), and 31.3% received adjuvant chemoradiation. The N stage was pathologically upstaged in 629 (20.9%) patients after TORS. Patients treated at higher-volume centers were more likely to have negative surgical margins (OR: 0.96, 95% CI: 0.94, 0.98, p &lt, 0.001), but this did not influence the receipt of adjuvant therapy. The high rate of adjuvant multimodality treatment after TORS suggests a need for improved patient selection. Limitations of this study, including lack of data on loco-regional control, progression free survival, acute and late toxicities, and utilization of pretreatment PET/CT imaging, should be addressed in future studies.

As elegant as is the concept upon which Boron Neutron Capture Therapy (BNCT) is based, unfortunately it has not gained widespread acceptance by the physicians who are treating cancer patients on a daily basis. The question is why? Very simply put, the clinical results obtained in treating patients with high grade gliomas and recurrent tumors of the head and neck region have not been convincing enough to produce more interest in BNCT as a cancer treatment modality. There are a variety of reasons for this, one of the most important of which has been its dependency on nuclear reactors as neutron sources. With the advent of accelerator based neutron sources (ABNS), this hopefully will be addressed. If the results obtained from ongoing and soon to be initiated clinical trials can at least demonstrate equivalency to those obtained with nuclear reactors, this should address the first problem. The second problem relates to boron delivery agents, and despite the considerable efforts of chemists and biologists over the past 50 years, there are only two drugs that currently are being used clinically, sodium borocaptate (BSH) and boronophenylalanine (BPA). It is widely recognized that these two drugs are less than ideal. Perhaps new and more effective boron delivery agents will finally appear on the scene, but barring that, we will address the question of what can be done now to make BNCT a more effective cancer treatment modality.

Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Vorinostat was administered at the assigned dosage level (100-400 mg, three times weekly) in a standard 3 + 3 dose escalation design. Vorinostat therapy began 1 week prior to initiation of standard, concurrent chemoradiation therapy and continued during the entire course of therapy. Results Twenty six patients met eligibility criteria and completed the entire protocol. The primary tumor sites included tonsil (12), base of tongue (9), posterior pharyngeal wall (1), larynx (4) and hypopharynx (3). Of the 26 patients, 17 were HPV-positive and 9 were HPV-negative. The MTD of Vorinostat was 300 mg administered every other day. Anemia (n = 23/26) and leukopenia (n = 20/26) were the most commonly identified toxicities. The most common Grade3/4 events included leukopenia (n = 11) and lymphopenia (n = 17). No patient had Grade IV mucositis, dermatitis or xerostomia. The median follow time was 33.8 months (range 1.6–82.9 months). Twenty four of 26 (96.2%) patients had a complete response to therapy. Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended.

Purpose To classify tumor imaging voxels at-risk for treatment failure within the heterogeneous cervical cancer using DCE MRI and determine optimal voxel's DCE threshold values at different treatment time points for early prediction of treatment failure. Material and Method DCE-MRI from 102 patients with stage IB2–IVB cervical cancer was obtained at 3 different treatment time points: before (MRI 1) and during treatment (MRI 2 at 2–2.5 weeks and MRI 3 at 4–5 weeks). For each tumor voxel, the plateau signal intensity (SI) was derived from its time-SI curve from the DCE MRI. The optimal SI thresholds to classify the at-risk tumor voxels was determined by the maximal area under the curve using ROC analysis when varies SI value from 1.0 to 3.0 and correlates with treatment outcome. Results The optimal SI thresholds for MRI 1, 2 and 3 were 2.2, 2.2 and 2.1 for significant differentiation between local recurrence/control, respectively, and 1.8, 2.1 and 2.2 for death/survival, respectively. Conclusion Optimal SI thresholds are clinically validated to quantify at-risk tumor voxels which vary with time. A single universal threshold (SI = 1.9) was identified for all 3 treatment time points and remained significant for the early prediction of treatment failure.

Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response.Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups.We identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p .001) and IR-RPA (97.1 vs 80.3%, p .001) groupings.When treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC.

BACKGROUND Several studies have demonstrated that omitting the routine use of adjuvant whole-brain radiation therapy for patients with newly diagnosed brain metastases may be a reasonable first-line strategy. Retrospective evidence suggests that fractionated stereotactic radiotherapy (fSRT) may have a lower level of toxicity with equivalent efficacy in comparison with radiosurgery. OBJECTIVE To study the phase II efficacy of using a focally directed treatment strategy for symptomatic brain metastases by the use of fSRT with or without surgery and omitting the routine use of adjuvant whole-brain radiation therapy. METHODS We used a Fleming single-stage design of 40 patients. Patients were eligible if they presented with 1 to 3 newly diagnosed symptomatic brain metastases, Karnofsky performance scale (KPS) greater than 60, and histological confirmation of primary disease. Patients underwent fSRT with the use of a dose of 30 Gy in 5 intensity-modulated fractions as primary or adjuvant treatment after surgical resection. The primary end point was the proportion of patients who experienced neurological death. Secondary end points were overall survival, time to KPS