Purpose: We previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Methods: Oligometastatic patients with ≤5 active metastases treated with either SIB or MA radiation at two institutions from 2013 to 2019 were analyzed retrospectively for treatment-related toxicity, pain control, and recurrence patterns. Tumor metastasis control (TMC) was defined as an absence of progression in the high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside the elective PTV but within the adjacent bone or nodal basin. Distant recurrence (DR) was defined as any recurrence that is not within the PTV or surrounding bone or nodal basin. The outcome rates were estimated using the Kaplan–Meier method and compared between the two techniques using the log-rank test. Results: 101 patients were treated via an SIB to 90 sites (58% nodal and 42% osseous) and via MA radiation to 46 sites (22% nodal and 78% osseous). The median follow-up among surviving patients was 24.6 months (range 1.4–71.0). Of the patients treated to MA, the doses ranged from 18 Gy in one fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with an SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No acute grade ≥3 toxicities occurred in either cohort. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis and two vertebral body compression), all related to the high dose PTV and not the elective volume. There was similar crude pain relief between cohorts. The MR-free survival rate at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (p = 0.07). The crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences in DR-free survival (65% (95% CI: 55–74%; p = 0.24)), disease-free survival (60% (95% CI: 40–75%; p = 0.40)), or overall survival (88% (95% CI: 73–95%; p = 0.26)), between the MA and SIB cohorts. Conclusion: Both SIB and MA irradiation of oligometastases achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for oligometastases treated with an SIB. Further investigation of this technique with prospective trials is warranted.

OBJECTIVES:To develop and validate a nomogram that predicts overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) vs. observation.MATERIALS AND METHODS:Adults with biopsy-proven T1-T2N0 NCSLC treated with SABR (30-70 Gy in 1-10 fractions with biologically effective dose ≥100 Gy10) or observation between 2004 and 2015 in the National Cancer Database (NCDB) were identified. Propensity score was used to match SABR and observation cohorts on prognostic demographic and clinicopathologic factors identified by logistic regression. Using backward selection, a multivariable Cox proportional hazard was identified predicting 2- and 5-year OS via a nomogram. Model prediction accuracy was assessed by time-dependent receiver operating characteristic (ROC) curves and integrated area under the ROC curve (AUC) analysis.RESULTS:A total of 22,073 adults met inclusion criteria and 4418 matched pairs (total n = 8836) were identified for nomogram development. The factors most strongly associated with improved OS on multivariable analysis included younger age (HR 0.82 by decade, P < .001), female sex (HR 0.81, P < .001), lower comorbidity index (HR 0.65 for 0 vs. ≥3, P < .001), smaller tumor size (HR 0.60 for ≤3 cm vs. 5.1-7 cm, P < .001), adenocarcinoma histology (P < .001), and receipt of SABR (P < .001). Interaction between SABR and histology was significantly associated with OS (P = .017). Relative to adenocarcinoma, patients with squamous cell carcinoma who were observed (HR 1.44, 95% CI 1.33-1.56) or treated with SABR (HR 1.24, 95% CI 1.14-1.35) had significantly worse OS. The nomogram demonstrated fair accuracy for predicting OS, with an integrated time-dependent AUC of 0.694 over the entire follow-up period.CONCLUSION:This nomogram estimates OS at 2 and 5 years based on whether medically inoperable early-stage NSCLC patients receive SABR or elect for observation. Incorporation of other variables not captured within the NCDB may improve the model accuracy.

Background Alveolar ridge squamous cell carcinoma (ARSCC) is poorly represented in randomized trials. Methods Adults in the National Cancer Database diagnosed with ARSCC between 2010 and 2014 who should be considered for postoperative radiotherapy (PORT) based on National Comprehensive Cancer Network (NCCN)-defined risk factors were identified. Results Eight hundred forty-five (58%) of 1457 patients meeting the inclusion criteria received PORT. PORT was associated with improved overall survival (OS) on unadjusted (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-0.98,P= .02) and multivariable (HR 0.78, 95% CI 0.64-0.94,P= .002) analyses. PORT was associated with significantly improved 5-year OS for patients with 1 (68% vs 58%,P < .001), 2 (52% vs 31%,P < .001), and >= 3 (38% vs 24%,P < .001) NCCN-defined risk factors. Prognostic variables significantly associated with worse OS on multivariable analysis included advanced age, primary tumor size >= 3 cm, high grade, positive margin(s), stage N2-3, level IV/V nodal metastasis, and extranodal extension. Conclusion PORT for resected ARSCC with adverse pathologic features is associated with significantly improved OS.

Background: Combining radiotherapy (RT) and immunotherapy (IT) may enhance outcomes for metastatic non-small cell lung cancer (mNSCLC). However, data on the immunomodulatory effects of extracranial RT remains limited. This retrospective database analysis examined real-world practice patterns, predictors of survival, and comparative effectiveness of extracranial radioimmunotherapy (RT + IT) versus early-incorporation immunotherapy (eIT) in patients with mNSCLC. Methods: Patients diagnosed with mNSCLC between 2004-2016 treated with eIT or RT + IT were identified in the National Cancer Database. Practice patterns were assessed using Cochrane-Armitrage trend test. Cox proportional hazards and Kaplan-Meier method were used to analyze overall survival (OS). Propensity score matching was performed to account for baseline imbalances. Biologically effective doses (BED) were stratified based on the median (39 Gy(10)). Stereotactic body radiotherapy (SBRT) was defined as above median BED in <= 5 fractions. Results: eIT utilization increased from 0.3% in 2010 to 13.2% in 2016 (P4.0001). Rates of RT + eIT increased from 38.8% in 2010 to 49.1% in 2016 among those who received eIT (P<0.0001). Compared to eIT alone, RT + eIT demonstrated worse median OS (11.2 vs. 13.2 months) while SBRT + eIT demonstrated improved median OS (25 vs. 13.2 months) (P<0.0001). There were no significant differences in OS based on sequencing of eIT relative to RT (log-rank P=0.4415) or irradiated site (log-rank P=0.1606). On multivariate analysis, factors associated with improved OS included chemotherapy (HR 0.86, P=0.0058), treatment at academic facilities (HR 0.83, P<0.0001), and SBRT (HR 0.60, P=0.0009); after propensity-score multivariate analysis, SBRT alone showed improved OS (HR 0.28, P<0.0001). Conclusions: Utilization of RT + eIT in mNSCLC is increasing. SBRT + eIT was associated with improved OS on propensity-score matched analysis. There were no significant differences in OS based on RT + eIT sequencing or site irradiated. Whether these observations reflect patient selection or possible immunomodulatory benefits of RT is unclear and warrants further study.

Both SIB and MA irradiation of OM achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for OM treated with SIB. Although more late grade 3 toxicities were seen in the SIB cohort, these were mechanistically related to the high dose PTV and not the elective volume, with differences in treated metastasis location/characteristics. Further investigation of this technique with prospective trials is warranted.

The radiologic appearance of locally advanced lung cancer may be linked to molecular changes of the disease during treatment, but characteristics of this phenomenon are poorly understood. Radiomics, liquid biopsy of cell-free DNA (cfDNA), and next-generation sequencing of circulating tumor DNA (ctDNA) encode tumor-specific radiogenomic expression patterns that can be probed to study this problem. Preliminary findings are reported from a radiogenomic analysis of CT imaging, cfDNA, and ctDNA in 24 patients (median age, 64 years; range, 49-74 years) with stage III lung cancer undergoing chemoradiation on a prospective pilot study (NCT00921739) between September 2009 and September 2014. Unsupervised clustering of radiomic signatures resulted in two clusters that were associated with ctDNA TP53 mutations (P = .03) and changes in cfDNA concentration after 2 weeks of chemoradiation (P = .02). The radiomic features dissimilarity (hazard ratio [HR] = 0.56; P = .05), joint entropy (HR = 0.56; P = .04), sum entropy (HR = 0.53; P = .02), and normalized inverse difference (HR = 1.77; P = .05) were associated with overall survival. These results suggest heterogeneous and low-attenuating disease without a detectable ctDNA TP53 mutation was associated with early surges of cfDNA concentration in response to therapy and a generally better prognosis. Keywords: CT-Quantitative, Radiation Therapy, Lung, Computer Applications-3D, Oncology, Tumor Response, Outcomes Analysis Clinical trial registration no. NCT00921739 Supplemental material is available for this article. © RSNA, 2021.

Objective: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. Methods: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. Results: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + Cr receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + Cr was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). Conclusions: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity. (C) 2019 Elsevier Inc. All rights reserved.

Background This report describes a process for designing a 3D printed patient-specific applicator for HDR brachytherapy of the orbit. Case presentation A 34-year-old man with recurrent melanoma of the orbit was referred for consideration of re-irradiation. An applicator for HDR brachytherapy was designed based on the computed tomography (CT) of patient anatomy. The body contour was used to generate an applicator with a flush fit against the patient’s skin while the planning target volume (PTV) was used to devise channels that allow for access and coverage of the tumor bed. An end-to-end dosimetric test was devised to determine feasibility for clinical use. The applicator was designed to conform to the volume and contours inside the orbital cavity. Support wings placed flush with the patient skin provided stability and reproducibility, while 16 source channels of varying length were needed for sufficient access to the target. A solid sheath, printed as an outer support-wall for each channel, prevented bending or accidental puncturing of the surface of the applicator. Conclusions Quality assurance tests demonstrated feasibility for clinical use. Our experience with available 3D printing technology used to generate an applicator for the orbit may provide guidance for how materials of suitable biomechanical and radiation properties can be used in brachytherapy.

The development of immune checkpoint inhibitors (ICPIs) has changed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). Despite compelling preclinical data suggesting a synergy between radiation therapy (RT) and ICPIs, robust clinical data on combination therapy is lacking. This retrospective study seeks to describe clinical outcomes for patients with metastatic NSCLC treated with RT prior to ICPI vs ICPI alone. All patients at our institution with stage IV NSCLC receiving ICPI (2015-2018) were retrospectively identified. Based on RT receipt ≤12 months prior to ICPI, 134 patients were assigned to one of two cohorts: ICPI alone (n=65) vs RT+ICPI (n=69). The primary endpoint was progression-free survival (PFS) calculated from initiation of ICPI. Secondary endpoints included overall survival (OS), toxicity (CTCAE v4.0), and patterns of progression. Factors known to independently correlate with OS and/or ICPI response were considered in a Cox proportional hazards model for PFS. The median age at initiation of ICPI was 68 years (35-88). Of those with PDL1 scores, 32 (34%) had 1-49% expression and 37 (39%) had ≥50% PDL1 expression. After a median follow-up of 5.5 months, median PFS for ICPI alone vs RT+ICPI was 6.1 months vs 2.8 months, respectively (log-rank p=0.03). Median OS was 21.4 months for ICPI alone vs not yet reached for RT+ICPI (HR=0.8, log rank p=0.46). RT status, performance status (PS) and prior systemic therapy were each significantly associated with PFS in univariate analyses; age, sex, smoking, histology, intra/extra-cranial, and oligometastatic disease were not associated. RT remained significantly related to PFS (HR 0.55, no RT vs RT; p=0.02) in a multivariable analysis adjusting for PS (HR 0.47, 0-1 vs 2-3; p=0.004) and prior systemic therapy (HR 0.55, no vs yes; p=0.03). No significant difference in toxicity rates was observed between ICPI (28.1%) and ICPI+RT (23.1%). There was no significant relationship between RT and subsequent pattern of progression (intra +/- extracranial, χ2 p=0.45; initial +/- new site; χ2 p=0.42). RT prior to ICPI does not significantly increase toxicity. In contrast to prior data, this study found a reduction in PFS when RT was given prior to ICPI, but no difference in OS. While this may reflect unadjusted imbalances or referral bias between the cohorts, the trend merits further analysis as to the optimal combination of RT and ICPI.

Background: Colorectal cancer is the third most common cancer in the United States and associated with significant morbidity and mortality. Within colorectal cancer histologies, squamous cell carcinomas (SCC) are rare compared to adenocarcinomas, with only about 200 cases reported to date. Because rectal SCC is rarely encountered, there is a lack of literature and clinical consensus surrounding its optimal treatment approach. Staging and management of SCC can be partly analogous to both rectal adenocarcinoma and anal canal SCC, which leads to a dilemma in how to best approach these patients. As large randomized prospective trials are unrealistic in the setting of this rare malignancy, this study evaluates an institutional experience and reviews the existing literature to help guide future management approaches. Methods: This retrospective study compared various treatment regimens for rectal SCC patients treated at Duke University Medical Center from January 1, 1980 through December 31, 2016. Patients ≥18 years old with histologically confirmed, nonmetastatic rectal SCC were included. Due to small sample size, all statistical analyses were descriptive. For our systematic review, a comprehensive search of PubMed from 1933 to March 2018 was performed, with selected articles referenced to ensure all relevant publications were included. A qualitative analysis was performed to examine patient diagnoses, treatments, and disease- and treatment-related outcomes. Results: Eight patients were included. Three patients underwent initial, curative attempt surgery and two of these patients required colostomy. With follow-up ranging from 7.1 to 31.5 months, one patient was alive with no evidence of disease while two developed local/regional recurrences. Five patients received definitive chemoradiation. Of these, three patients developed local/regional and/or metastatic recurrence. Two patients achieved complete response on imaging and currently remain disease-free (follow-up of 31.5 and 33.6 months). Conclusions: Although the review of our institutional experience is limited by small numbers, our analysis suggests that definitive chemoradiation therapy is the preferred treatment approach to rectal SCC based on improved disease-related outcomes, sphincter preservation and morbidity profiles. This conclusion is supported by a systematic literature review.

Purpose: To perform a multi-institutional analysis of patients with synchronous prostate and rectosigmoid cancers. Materials and Methods: A retrospective review of Duke University and Durham Veterans Affairs Medical Center records was performed for men with both prostate and rectosigmoid adenocarcinomas from 1988 to 2017. Synchronous presentation was defined as symptoms, diagnosis, or treatment of both cancers within 12 months of each other. The primary study endpoint was overall survival. Univariate and multivariable Cox regression was performed. Results: Among 31,883 men with prostate cancer, 330 (1%) also had rectosigmoid cancer and 54 (16%) of these were synchronous. Prostate cancer was more commonly the initial diagnosis (59%). Fifteen (28%) underwent prostatectomy or radiotherapy before an established diagnosis of rectosigmoid cancer. Stage I, II-III, or IV rectosigmoid cancer was present in 26, 57, and 17% of men, respectively. At a median follow-up of 43 months, there were 18 deaths due rectosigmoid cancer and two deaths due to prostate cancer. Crude late grade ≥3 toxicities include nine (17%) gastrointestinal and six (11%) genitourinary. Two anastomotic leaks following low anterior resection occurred in men who received a neoadjuvant radiotherapy prostate dose of 70.6-76.4 Gy. Rectosigmoid cancer stages II-III (HR 4.3, p = 0.02) and IV (HR 16, p < 0.01) as well as stage IV prostate cancer (HR 31, p < 0.01) were associated with overall survival on multivariable analysis. Conclusions: Synchronous rectosigmoid cancer is a greater contributor to mortality than prostate cancer. Men aged ≥45 with localized prostate cancer should undergo colorectal cancer screening prior to treatment to evaluate for synchronous rectosigmoid cancer.

The incidence of rectal cancer in adolescents and young adults (AYA) is increasing. While randomized trials in older adults have established neoadjuvant radiotherapy (nRT) as a standard treatment for stage II-III disease, there is limited evidence supporting this regimen in AYA. We hypothesized that AYA with rectal cancer have a different underlying biology and response to nRT compared to older adults. To investigate this, we conducted a database study comparing clinicopathologic features at diagnosis and response to treatment in AYA vs older adults with stage II-III rectal adenocarcinoma. Patients diagnosed with stage II-III rectal adenocarcinoma between 2004-2016 were identified in the National Cancer Database. Early-onset (EO-RC) and late-onset rectal cancer (LO-RC) were defined as aged 15-39 and 40-90 at diagnosis. For overall survival (OS) analyses, the LO-RC cohort was subdivided into middle-onset (age 40-65) and late-onset (age 66-90) groups to adjust for differences in life expectancy and selection bias. Chi-squared and t-tests were used to compare clinicopathologic features between groups. Unadjusted OS was estimated using the Kaplan-Meier method, with groups compared by log-rank test. Of 55,093 patients with stage II-III rectal adenocarcinoma, 2,785 (5%) had EO-RC. Patients with EO-RC had fewer comorbidities (7% vs 21% Charlson/Deyo score ≥1, p<0.001) and presented with more advanced disease at diagnosis, including a higher rate of nodal metastases (53% vs 41%, p<0.001). Among patients who received nRT, those with EO-RC had similar rates of pathologic complete response (11% vs 12%, p = 0.17) and sphincter-preserving resection (71% vs 71%, p = 0.56) compared to LO-RC, but were slightly less likely to have pathologic downstaging of the primary tumor (47% vs 50%, p = 0.04) and nodal metastases (60% vs 66%, p<0.001). The EO-RC cohort had better 90-day post-operative mortality (0.3% vs 1.6%, p<0.001) than the LO-RC cohort. Unadjusted OS analyses showed that nRT receipt was not associated with OS in early-onset or middle-onset patients (p>0.05); however, nRT was associated with improved OS in LO-RC patients (p<0.001). The estimated 10-year OS for patients aged 15-39, 40-65, and 66-90 at diagnosis was 67%, 60%, and 37%, respectively (p<0.001). AYA with stage II-III rectal adenocarcinoma were more likely to present with nodal metastases, slightly less likely to have pathologic downstaging following nRT, and demonstrated no OS benefit from nRT as compared to older adults. Since AYA have fewer medical comorbidities and higher long-term survival, they may be at increased risk of late radiation-related toxicities. Further research to appropriately identify a cost-effective screening strategy in high-risk AYA is crucial to decrease morbidity and mortality.

There is a paucity of data to guide management of patients with inoperable stage IIB (American Joint Committee on Cancer eighth edition) non small-cell lung cancer. Practice patterns and comparative effectiveness analyses were performed for 10,081 adults in the National Cancer Database diagnosed between 2004 and 2015 and treated with stereotactic body radiotherapy, hypofractionated radiotherapy, or conventionally fractionated radiotherapy. Stereotactic body radiotherapy utilization for T3N0M0 non small-cell lung cancer is increasing rapidly and was associated with improved survival. Background: The purpose of this study was to analyze practice patterns and perform comparative effectiveness of definitive radiotherapy techniques for inoperable stage IIB (American Joint Committee on Cancer eighth edition) non-small-cell lung cancer (NSCLC). Materials and Methods: Adults in the National Cancer Database diagnosed with T3N0M0 or T1-2N1M0 NCSLC between 2004 and 2015 who received definitive radiotherapy were identified. Cases were divided as stereotactic body radiotherapy (SBRT), hypofractionated radiotherapy (HFRT), or conventionally fractionated radiotherapy (CFRT) and stratified by systemic therapy (ST). Cox proportional hazards models evaluated the effect of covariates on overall survival (OS). Subgroup analysis by tumor size, chest wall invasion, multifocality, and ST use was performed with Kaplan-Meier estimates of OS. Results: A total of 10,081 subjects met inclusion criteria: 4401 T3N0M0 (66.5% CFRT, 11.0% HFRT, and 22.5% SBRT) and 5680 T1-2N1M0 (92.5% CFRT and 7.5% HFRT). For T3N0M0 NSCLC, SBRT utilization increased from 3.7% in 2006% to 35.4% in 2015. Subjects treated with SBRT were more likely to have smaller tumors, multifocal tumors, or adenocarcinoma histology. SBRT resulted in similar or superior OS compared with CFRT for tumors > 5 cm, tumors invading the chest wall, or multifocal tumors. SBRT was significantly associated with improved OS on multivariate analysis (hazard ratio, 0.715; P < .001). For T1-2N1M0 NSCLC, patients treated with HFRT were significantly older and less likely to receive ST; nevertheless, there was no difference in OS between HFRT and CFRT on multivariate analysis. Conclusion: CFRT + ST is utilized most frequently to treat stage IIB NSCLC in the United States when surgery is not performed, though it is decreasing. SBRT utilization for T3N0M0 NSCLC is increasing and was associated with improved OS. (C) 2019 Elsevier Inc. All rights reserved.

PURPOSE:Concurrent chemoradiation therapy (CRT) is the principal treatment modality for locally advanced lung cancer. Cell death due to CRT leads to the release of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) into the bloodstream, but the kinetics and characteristics of this process are poorly understood. We hypothesized that there could be clinically meaningful changes in cfDNA and ctDNA during a course of CRT for lung cancer. METHODS AND MATERIALS:Multiple samples of plasma were obtained from 24 patients treated with CRT for locally advanced lung cancer to a mean dose of 66 Gy (range, 58-74 Gy) at the following intervals: before CRT, at weeks 2 and 5 during CRT, and 6 weeks after treatment. cfDNA was quantified, and a novel next generation sequencing (NGS) technique using enhanced tagged/targeted-amplicon sequencing was performed to analyze ctDNA. RESULTS:Patients for whom specific mutations in ctDNA were undetectable at the baseline time point had improved survival, and potentially etiologic driver mutations could be tracked throughout the course of CRT via NGS in multiple patients. We quantified the levels of cfDNA from patients before CRT, at week 2, week 5, and at 6 weeks after treatment. No differences were observed at weeks 2 and 5 of therapy, but we noted a significant increase in cfDNA in the posttreatment follow-up samples compared with samples collected before CRT (P = .05). CONCLUSIONS:Dynamic changes in both cfDNA and ctDNA were observed throughout the course of CRT in patients with locally advanced lung cancer. Specific mutations with therapeutic implications can be identified and tracked using NGS methodologies. Further work is required to characterize the changes in cfDNA and ctDNA over time in patients treated with CRT and to assess the predictive and prognostic potential of this powerful technology.

Purpose: To assess whether radiographic and metabolic changes on midchemoradiation therapy (CRT) fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) for cervical cancer predict outcome. Methods and Materials: Women with International Federation of Gynecology and Obstetrics stage IB1-IVB cervical cancer treated with concurrent cisplatin-based CRT and brachytherapy were enrolled on a single-institution prospective clinical trial; FDG-PET/CT was obtained before CRT and at 30 to 36 Gy. Max and mean standard uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) for the primary tumor and clinically involved lymph nodes from the pre-CRT and intra-CRT FDG-PET/CT were recorded. Clinical endpoints analyzed include overall survival (OS), disease-free survival (DFS), and rates of cervical recurrence (CR), nodal recurrence (NR), and distant metastasis (DM). FDG-PET/CT variables and other prognostic factors associated with clinical endpoints were identified via univariate Cox proportional hazards modeling and competing risk analysis. Results: Thirty women were enrolled from 2012 to 2016. After a median follow-up of 24 months, 2-year rates of OS, DFS, DM, NR, and CR were 68% (95% confidence interval [CI], 51%-85%), 44% (95% CI, 26%-63%), 42% (95% CI, 23%-59%), 14% (95% CI, 4%-30%), and 10% (95% CI, 2%-24%), respectively. Intra-PET metrics and TLG across all PET scans were most consistently associated with OS, DFS, DM, and NR on univariate analysis. Intra-CRT TLG was associated with OS (hazard ratio [HR] 1.35; 95% CI, 1.15-1.55; P = .001), DFS (HR 1.19; 95% CI, 1.04-1.34; P = .018), and NR (HR 1.25; 95% CI, 1.10-1.40; P = .002). No absolute or relative changes between parameters of baseline and mid-CRT FDG-PET/CT were associated with disease outcomes on univariate analysis, with the exception of relative change in mean standard uptake values and CR (P = .004). Conclusions: In this group of patients with high-risk cervical cancer treated with CRT and brachytherapy, TLG and metabolic tumor volume on intra-CRT FDG-PET/CT was associated with OS. These metrics may provide an early signal for selective treatment intensification with either dose escalation or adjuvant chemotherapy. (C) 2019 Elsevier Inc. All rights reserved.

Purpose: To perform a multi-institutional analysis following treatment of limited osseous and/or nodal metastases in patients using a novel hypofractionated image-guided radiotherapy with simultaneous-integrated boost (HIGRT-SIB) technique. Methods: Consecutive patients treated with HIGRT-SIB for ≤5 active metastases at Duke University Medical Center or Durham Veterans' Affairs Medical Center between 2013 and 2018 were analyzed to determine toxicities and recurrence patterns following treatment. Most patients received 50 Gy to the PTVboost and 30 Gy to the PTVelect simultaneously in 10 fractions. High-dose treatment volume recurrence (HDTVR) and low-dose treatment volume recurrence (LDTVR) were defined as recurrences within PTVboost and PTVelect, respectively. Marginal recurrence (MR) was defined as recurrence outside PTVelect, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as recurrences not meeting HDTVR, LDTVR, or MR criteria. Freedom from pain recurrence (FFPR) was calculated in patients with painful osseous metastases prior to HIGRT-SIB. Outcome rates were estimated at 12 months using the Kaplan-Meier method. Results: Forty-two patients met inclusion criteria with 59 sites treated with HIGRT-SIB (53% nodal and 47% osseous). Median time from diagnosis to first metastasis was 31 months and the median age at HIGRT-SIB was 69 years. The most common primary tumors were prostate (36%), gastrointestinal (24%), and lung (24%). Median follow-up was 11 months. One acute grade ≥3 toxicity (febrile neutropenia) occurred after docetaxel administration immediately following HIGRT-SIB. Four patients developed late grade ≥3 toxicities: two ipsilateral vocal cord paralyzes and two vertebral compression fractures. The overall pain response rate was 94% and the estimated FFPR at 12 months was 72%. The estimated 12 month rate of HDTVR, LDTVR, MR, and DR was 3.6, 6.2, 7.6, and 55.8%, respectively. DR preceded MR, HDTVR, or LDTVR in each instance. The estimated 12 month probability of in-field and marginal control was 90.0%. Conclusion: Targeting areas at high-risk for occult disease with a lower radiation dose, while simultaneously boosting gross disease with HIGRT in patients with limited osseous and/or nodal metastases, has a high rate of treated metastasis control, a low rate of MR, acceptable toxicity, and high rate of pain palliation. Further investigation with prospective trials is warranted.

Letters17 September 2019Radiotherapy and Small Cell Carcinoma With Paraneoplastic Polyneuropathy: A Case ReportBrahma D. Natarajan, MD, Corbin D. Jacobs, MD, and Joseph K. Salama, MDBrahma D. Natarajan, MDDuke University, Durham, North Carolina (B.D.N., C.D.J., J.K.S.)Search for more papers by this author, Corbin D. Jacobs, MDDuke University, Durham, North Carolina (B.D.N., C.D.J., J.K.S.)Search for more papers by this author, and Joseph K. Salama, MDDuke University, Durham, North Carolina (B.D.N., C.D.J., J.K.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0236 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Small cell carcinoma is an aggressive cancer known for early and rapid metastasis. Standard treatment involves platinum-based chemotherapy combined with radiotherapy, which provides a median survival of 18 to 24 months (1). Paraneoplastic neurologic syndromes are rare (0.01% of patients with cancer), but when they do occur are often associated with small cell carcinoma (2).Objective: To alert clinicians to the possibility that radiotherapy alone might effectively treat patients with extrapulmonary small cell carcinoma and a paraneoplastic neurologic syndrome.Case Report: A 71-year-old man first presented with unintentional weight loss. He had never used tobacco. He was subsequently diagnosed ...References1. Walenkamp AM, Sonke GS, Sleijfer DT. Clinical and therapeutic aspects of extrapulmonary small cell carcinoma. Cancer Treat Rev. 2009;35:228-36. [PMID: 19068273] doi:10.1016/j.ctrv.2008.10.007 CrossrefMedlineGoogle Scholar2. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349:1543-54. [PMID: 14561798] CrossrefMedlineGoogle Scholar3. Lee CM, Lee JD, Hobson-Webb LD, et al. Treatment of thymoma-associated myasthenia gravis with stereotactic body radiotherapy: a case report. Ann Intern Med. 2016;165:300-1. [PMID: 26974367]. doi:10.7326/L15-0469 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Duke University, Durham, North Carolina (B.D.N., C.D.J., J.K.S.)Acknowledgment: The authors thank Dr. Brandon Howard for his assistance in obtaining the PET images.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0236.This article was published at Annals.org on 25 June 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 September 2019Volume 171, Issue 6Page: 440-441KeywordsMyelodysplastic syndromesNeuropathyPatient advocacyPositron emission tomographyReflexesResearch laboratoriesSpineThymomaWeight lossWheelchairs ePublished: 25 June 2019 Issue Published: 17 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Lymph node involvement and the number of positive nodes is a significant prognosticator in oral cavity cancers and current staging system does not incorporate it as an integral part.This was a retrospective study of oral cavity cancer patients who were operated during the time period of 2009–2017. The data was collected and analysed to assess the impact of increase in the number of positive nodes on survival and its comparison of survival statistics to current AJCC staging.A total of 1431 patients were included in this study and 32.5% of these patients had a node positive disease. Nodal positivity was a significant prognosticator on multivariate analysis. Number of positive nodes was modelled with restricted cubic spline function and it showed progressive worsening of survival functions with increase in number. On Kaplan Meier analysis there was a better separation of curves when number of positive nodes was used and Akaike information criterion (AIC) showed that it was a better prognosticator than existing AJCC staging.Number of positive nodes is a significant prognosticator of prognosis and hence should be considered in the AJCC staging system.

Increased access to stereotactic radiosurgery (SRS) to treat brain metastases (BM) has prompted reassessment of whole brain radiotherapy (WBRT) indications. A patterns of care analysis of various WBRT dose-fractionations for the U.S. in the era of SRS was performed. Adults in the National Cancer Database with BM at diagnosis of a lung, breast, skin, urogenital, gastrointestinal, or head/neck primary tumor between 2010-2015 and no prior malignancy were identified. WBRT was defined as 20-50 Gy to the brain in 4-44 fractions (fx) at 1.6-6 Gy/fx totaling 60-100 Gy2 biologically equivalent dose, administered in ≤60 days using a non-SRS external beam modality. SRS was defined as radiosurgery modality, 12-24 Gy/1 fx, 18-30 Gy/2 fx, 21-36 Gy/3 fx, 21-36 Gy/4 fx, or 25-40 Gy/5 fx to the brain. Short (ShWBRT), standard (StWBRT), and extended (ExWBRT) courses were defined as <10, 10-15, and >15 fx, respectively. Odds ratios (OR) of ShWBRT or ExWBRT receipt relative to StWBRT were calculated from multivariate logistic regression. Yearly utilization trends were analyzed with linear regression. 90388 subjects with BM at diagnosis were identified, the majority with primary lung cancer (83.0%). Of these, 24262 (26.8%) received WBRT and 11486 (12.7%) received SRS. 374 (0.4%) subjects received >10 fx and were reported to have received a radiosurgery modality, potentially reflecting combination WBRT and SRS, and were excluded from WBRT analysis. Annual use of WBRT decreased from 27.8% in 2010 to 23.5% in 2015, whereas annual use of SRS increased from 8.7% in 2010 to 17.9% in 2015. The most common WBRT dose-fractionations were 30 Gy/10 fx (56.8%), 37.5 Gy/15 fx (15.5%), and 35 Gy/14 fx (11.0%). 1020 (4.2%), 22356 (92.1%), and 886 (3.7%) received ShWBRT, StWBRT, and ExWBRT, respectively. StWBRT was the most frequently used fractionation for all primary sites. There was a significant reduction in use of ExWBRT (slope = -22.4%/yr, R2 = 0.97, p<0.01) between 2010-2015. No significant trends were identified for use of ShWBRT or StWBRT. On multivariate analysis, factors associated with significantly higher usage of ShWBRT were no chemotherapy receipt (OR 3.5, 95% CI 3.1-4.1, p<0.01), Medicaid compared to private insurance (OR 1.4, 95% CI 1.1-1.8, p<0.01), and treatment at academic centers (OR 1.3, 95% CI 1.1-1.6, p<0.01). On multivariate analysis, factors associated with significantly higher usage of ExWBRT were chemotherapy receipt (OR 1.2, 95% CI 1.0-1.4, p=0.03) and treatment at comprehensive community cancer centers (OR 1.7, 95% CI 1.4-2.0, p<0.01). WBRT utilization to treat BM at diagnosis in the U.S. has decreased, especially >15 fx regimens. Choosing Wisely’s recommendation in Sept 2014 to not add WBRT to SRS may have influenced the observed trends. WBRT in 10-15 fx was the most common regimen for all primary tumors analyzed. WBRT in <10 fx was used much more frequently in those who did not receive chemotherapy, likely due to poor performance status.