Complete Pathologic Response to Neoadjuvant Chemoimmunotherapy and Oxaliplatin-Induced Fever Associated With IL-6 Release in a Patient With Locally Advanced Colon Cancer

Neoadjuvant systemic therapy is a preferred treatment approach for a number of tumor types due to many potential advantages over upfront surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. For colon cancer, current standard of care is upfront surgery followed by adjuvant systemic therapy in high-risk patients. Concerns about inaccurate radiological staging and tumor progression during preoperative treatment, as well the lack of randomized data demonstrating benefit, are among the reasons for the limited use of neoadjuvant therapy in this disease. Locally advanced colon cancer, defined as primary colon cancer with direct invasion into the adjacent structures or extensive regional lymph node involvement, is not always amenable to pathological complete resection, and when attempted it comes with high incidence of postoperative morbidity and mortality because of the required multivisceral resection. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been promising with downstaging of disease and higher rates of R0 resection. Here, we report a case of a patient with locally advanced, unresectable, mismatch repair deficient sigmoid colon cancer who was treated with neoadjuvant chemoimmunotherapy followed by surgical resection leading to a complete pathologic response after preoperative systemic chemoimmunotherapy.

Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy.

INTRODUCTION: Risk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade 2-3 endometrial cancer with deep myometrial invasion who were treated with vaginal brachytherapy as sole adjuvant therapy after hysterectomy and lymph node dissection. METHODS: We retrospectively reviewed the records of stage I patients with grade 2-3 endometrioid histology and ≥50% myometrial invasion treated at an academic institution from January 2005 to December 2017. Only patients with endometrioid histology were included. Mixed histologies, including papillary serous or clear cell components, were excluded. Further exclusion criteria were International Federation of Gynecology and Obstetrics stage IB grade 1 patients, follow-up time less than 3 months, receipt of pelvic irradiation or any form of systemic therapy (chemotherapy, aromatase inhibitor). Overall survival, disease-free survival, and pelvic recurrence-free survival were calculated with Kaplan-Meier methods. Multivariable Cox proportional hazards regression was used to analyze factors associated with overall survival and disease-free survival. RESULTS: Among 131 consecutive patients identified, 111 (85%) patients met the inclusion criteria. The majority (98.2%) underwent lymph node dissection with ≥10 lymph nodes removed in 78.9%. With a median follow-up of 36 months (IQR 12-70 months), the 3-year overall survival, disease-free survival, and pelvic recurrence-free survival were 89.6%, 90.1%, and 92.8%, respectively. Histologic grade 3, older age, and lymphovascular invasion were not associated with inferior outcomes; however, lower uterine segment involvement (p=0.031), tumor size >4 cm (p=0.024), and <10 lymph nodes removed (p=0.032) were associated with reduced disease-free survival on multivariable analysis. Pelvic recurrence occurred in 12 (11%) patients, most often in the setting of synchronous distant disease (n=9), and was significantly more likely with lower uterine segment involvement. CONCLUSION: Among patients with stage IB grade 2-3 endometrial cancer treated with vaginal brachytherapy, the risk factors for recurrence (larger tumor size and lower uterine segment involvement) in conjunction with established risk factors (high grade, ≥50% myometrial invasion, and lymphovascular invasion) may identify a group of high-risk patients who might benefit from pelvic radiotherapy.

Radiation therapy treatment facility and overall survival in the adjuvant setting for locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Treatment at high-volume surgical facilities (HVSFs) provides a survival benefit for patients with head and neck squamous cell carcinomas (HNSCCs); however, it is unknown what role postoperative radiation therapy (PORT) plays in achieving the improved outcomes. METHODS: From the National Cancer Database, 6844 patients with locally advanced invasive HNSCCs of the oral cavity, oropharynx, larynx, and hypopharynx who underwent definitive surgery with PORT between 2004 and 2013 were identified. HVSFs were those in the top percentile for annual case volume during this period. RESULTS: The median follow-up was 54 months. Compared with a lower volume surgical facility (LVSF), an HVSF improved 5-year overall survival (OS; 57.7% at HVSFs vs 52.5% at LVSFs; P = .0003). Overall, 31.6% of the patients changed their radiation therapy (RT) facility after surgery, with this being more common at HVSFs (39.1% vs 28.9% at LVSFs; P < .001). Among those patients undergoing surgery at an HVSF, remaining at the same facility for RT improved 5-year OS (63.1% vs 49.3% with a facility change; P < .0001). A propensity score-matched cohort of patients treated at HVSFs confirmed the improved 5-year OS when patients remained at the treating HVSF for RT (59.2% vs 50.7% with a facility change; P = .005). In a multivariate analysis, treatment at an HVSF and remaining there for RT resulted in a reduced hazard of death (hazard ratio, 0.81; 95% confidence interval, 0.69-0.94; P = .006). CONCLUSIONS: The survival benefit associated with HVSFs persists only when patients remain at the facility for RT, and this suggests that facility specialization and/or high-volume PORT may assist in driving the OS improvement.

The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma.

BACKGROUND: Extranodal (or extracapsular) extension (ENE) is an adverse prognostic factor in patients with head and neck cancers who undergo primary surgery. However, the significance of ENE in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is not well established, and single-institution studies have not established that ENE predicts inferior outcome. The authors investigated the prognostic value of ENE in HPV-positive patients who underwent primary surgery and whether adjuvant chemoradiation improved overall survival (OS) compared with radiation alone in ENE-positive patients. METHODS: Patients who underwent primary surgery for pathologic T1 (pT1) through pT4 tumors, pathologic N1 (pN1) through pN3 lymph node status, HPV-positive OPSCC were identified in the National Cancer Data Base from 2010 through 2012. Features associated with ENE were analyzed. Univariable and multivariable Cox regression analyses identified predictors of OS. The effect of adjuvant treatment on OS in ENE-positive cohort was also evaluated. RESULTS: In total, 1043 patients met inclusion criteria, among whom 43.5% were ENE-positive. Of the ENE-positive patients who had treatment details available, 72% received concurrent chemoradiotherapy, 16% received radiotherapy, and 12% received no adjuvant treatment. After a median follow-up of 28.4 months, ENE was associated with worse 3-year OS (89.3% vs 93.6%; P = .01). On multivariable analysis that included involved lymph nodes, only ENE, lymphovascular invasion, pT3/pT4 tumors, and Charlson-Deyo score were associated with worse OS. Among ENE-positive patients, there was no difference in 3-year OS between those who received adjuvant concurrent chemoradiotherapy versus radiotherapy alone (89.6% vs 89.3%, respectively; P = .55). Propensity score-matched comparison revealed similar results. CONCLUSIONS: ENE is associated with inferior OS in patients with HPV-positive OPSCC. However, OS was not better with adjuvant chemoradiotherapy compared with radiotherapy alone in ENE-positive patients. The current findings support the need for prospective studies of adjuvant chemoradiation in HPV-positive patients with ENE. Cancer 2017;123:2762-72. © 2017 American Cancer Society.

Evaluation of a sequential multi-modality imaging algorithm for the diagnosis of acute appendicitis in the pregnant female.

The purpose of this study is to evaluate the performance of a sequential multi-modality imaging algorithm for diagnosing acute appendicitis in pregnancy. This IRB-approved, HIPAA compliant study included 127 consecutive pregnant patients imaged for suspected appendicitis between October 2007 and May 2012; all patients initially underwent ultrasound (US) examination, followed by magnetic resonance imaging (MRI) if results of US were negative or equivocal. Computerized tomography (CT) was reserved for cases with inconclusive US and MRI results. The EMR was reviewed, recording results of imaging examinations and clinical outcomes. The diagnostic performance of this sequential multi-modality imaging algorithm was calculated with pathology correlation. Two (1.9 %) of the 127 US examinations reported suspected appendicitis; 125 (98.4 %) were inconclusive. Of the 125 patients with inconclusive US examinations, 103 underwent MRI, of which eight (6.2 %) demonstrated findings of acute appendicitis. Of the 103 patients that received MRI, nine (8.7 %) underwent CT. One patient had a CT performed directly after an inconclusive US exam. No additional cases of appendicitis were detected with CT. The sensitivity and specificity of US alone was 12.5 and 99.2 %, respectively; MRI was 100 and 93.6 %; the sequential multi-modality modality algorithm including US, CT, and MRI was 100 and 98.3 %. The diagnostic performance of this sequential multi-modality imaging algorithm for diagnosing acute appendicitis in pregnancy is high. Given the low yield of US, MRI should be considered the first-line imaging test. Although CT was employed in a small fraction of inconclusive MRI examinations, it still has a role in the diagnostic work-up of the pregnant patient with suspected appendicitis.

Hazardous Attitudes: Physician Decision Making in Radiation Oncology.

Purpose: The Federal Aviation Administration quantifies hazardous attitudes (HAs) among pilots using a scale. HAs have been linked to aviation risk. We assessed the influence of HAs and other factors in treatment decision making in radiation oncology (RO). Methods and Materials: An anonymous survey was sent to 809 radiation oncologists in US cities housing the top 25 cancer centers. The survey included an HA scale adapted for RO and presented 9 cases assessing risk-tolerant radiation therapy prescribing habits and compliance with the American Society for Radiation Oncology's Choosing Wisely recommendations. Demographic and treatment decision data were dichotomized to identify factors associated with prescribing habits using univariable and multivariable (MVA) logistic regression analyses. Results: A total of 139 responses (17.1%) were received, and 103 were eligible for analysis. Among respondents, 40% were female, ages were evenly distributed, and 83% were in academics. Median scores for all attitudes (macho, anti-authority, worry, resignation, and impulsivity) were below the aviation thresholds for hazard and data from surgical specialties. On MVA, responders >50 years old with >5 years' experience were 4.45 times more likely to recommend risk-tolerant radiation (P = .016). Macho attitude was negatively associated with Choosing Wisely compliant treatments (odds ratio [OR], 0.12; P = .001). Physicians who reported having previously retreated the supraclavicular fossa without complication were more likely to recommend retreatment in medically unfit patients if they felt the complication was avoided owing to careful planning (OR, 5.2; P = .008). Conclusions: To our knowledge, this represents the first study analyzing physician attitudes in RO and their effect on self-reported treatment decisions. This work suggests that attitude may be among the factors that influence risk-tolerant prescribing practices and compliance with Choosing Wisely recommendations.

An Evaluation of Health Numeracy among Radiation Therapists and Dosimetrists.

PURPOSE: Medical errors in radiation oncology sometimes involve tasks reliant on practitioners' grasp of numeracy. Numeracy has been shown to be suboptimal across various health care professionals. Herein, we assess health numeracy among American Society of Radiologic Technologists (ASRT) members. METHODS AND MATERIALS: The Numeracy Understanding for Medicine instrument (NUMi), an instrument to measure numeracy in the general population, was adapted to oncology for this study and distributed to ASRT members (n = 14,228) in 2017. Per NUMi scoring, health numeracy scores were categorized as low (0-7), low average (8-12), high average (13-17), or high (18-20). The impact of cGy versus Gy on numeracy performance was investigated. Spearman's rho and a Wilcox-Mann-Whitney test were used for comparisons between the different groups. RESULTS: A total of 662 eligible participants completed the instrument and identified as radiation oncology professionals. In the cGy and Gy NUMi scores, approximately 2% of respondents scored low-average, approximately 40% scored high-average, and approximately 58% scored high, with a median score of 18.0. Although the optimum NUMi score for ASRT members is unknown, one might expect our cohort to have numeracy skills at least as high as college freshmen. Roughly one-sixth of our study group scored at or below the average score of college freshmen (NUMi = 15). In the subset analysis of NUMi questions pertaining to radiation dose unit (cGy vs Gy), respondents performed better with cGy (mean score: 2.94; range, 2-3) versus Gy (mean: 2.91; range, 0-3; P = .011). CONCLUSIONS: In this study of limited sample size, overall numeracy is quite good compared with the general population. However, the range of scores is wide, and some respondents have lower scores that may be concerning, suggesting that numeracy may be an issue that requires improvement for a subset of the studied cohort. Performance was superior with the unit cGy; thus, the adoption of cGy as the standard unit is reasonable.

A Blinded, Prospective Study of Error Detection During Physician Chart Rounds in Radiation Oncology.

PURPOSE: Peer review during physician chart rounds is a major quality assurance and patient safety step in radiation oncology. However, the effectiveness of chart rounds in detecting problematic treatment plans is unknown. We performed a prospective blinded study of error detection at chart rounds to clarify the effectiveness of this quality assurance step. METHODS AND MATERIALS: Radiation Oncology Incident Learning System publications were queried for problematic plans approved for treatment that would be detectable at chart rounds. A resident physician, physicist, and dosimetrist collaboratively generated 20 treatment plans with simulated errors identical in nature to those reported to the Radiation Oncology Incident Learning System. These were inserted randomly into weekly chart rounds over 9 weeks, with a median of 2 problematic plans presented per chart rounds (range, 1-4). Data were collected on detection, attendance, length, and number of cases presented at chart rounds. Data were analyzed using descriptive statistics and univariable logistic regression with odds ratios. RESULTS: The median length of chart rounds over the study period was 60 minutes (range, 42-79); median number of cases presented per chart rounds was 45 (range, 38-50). The overall detection rate was 55% (11 of 20). Detection rates were higher for cases presented earlier in chart rounds: 75% versus 25% of problematic plans were detected within 30 minutes of start of chart rounds versus after 30 minutes (odds ratio, 0.11; 95% confidence interval, 0.01-0.88; P = .037). Detection rates showed a trend toward increase during the study period but this was not significant: 33% in weeks 1 to 5 and 73% during weeks 6 to 9 (5.3; 95% confidence interval, 0.78-36; P = .08). CONCLUSIONS: The detection of clinically significant problematic plans during chart rounds could be significantly improved. Problematic plans are more frequently detected earlier in chart rounds and inserting such plans into chart rounds may enhance detection; however, larger studies are needed to confirm these findings. A multi-institutional study is planned.

Adjuvant external beam radiotherapy for surgically resected, nonmetastatic anaplastic thyroid cancer.

BACKGROUND: EBRT in resected, nonmetastatic anaplastic thyroid cancer (ATC) remains undefined. We evaluated patterns/outcomes with EBRT and chemotherapy in this setting. METHODS: This retrospective analysis included patients identified from the National Cancer Database with nonmetastatic ATC from 2004 to 2014 who underwent non-palliative resection. RESULTS: Our analysis included 496 patients, including 375 who underwent adjuvant EBRT (among whom 198 received concurrent chemotherapy). The median age was 68 years. On MVA, EBRT was associated with sex (OR 0.5, 95% CI 0.3-0.8, P = .002) and income (OR 2.2, 95% CI 1.4-3.3, P < .001). EBRT was associated with longer OS on UVA (12.3 vs 9.1 months, P = .004) and MVA (HR 0.7 [CI 0.6-0.9], P = .004). Concurrent chemoradiation was associated with longer OS on UVA (14.0 vs 9.1 months, P = .003) and MVA (HR 0.6 [CI 0.5-0.8], P < .001). CONCLUSION: Adjuvant EBRT is associated with longer OS in resected, nonmetastatic ATC, with additional improved survival with concurrent chemotherapy.

Overall survival is improved when DCIS accompanies invasive breast cancer.

Invasive ductal carcinoma (IDC) often presents alone or with a co-existing ductal carcinoma in situ component (IDC + DCIS). Studies have suggested that pure IDC may exhibit different biological behavior than IDC + DCIS, but whether this translates to a difference in outcomes is unclear. Here, utilizing the National Cancer Database we identified 494,801 stage I-III breast cancer patients diagnosed with either IDC alone or IDC + DCIS. We found that IDC + DCIS was associated with significantly better overall survival (OS) compared to IDC alone (5-year OS, 89.3% vs. 85.5%, p < 0.001), and this finding persisted on multivariable Cox modeling adjusting for demographic, clinical, and treatment-related variables. The significantly superior OS observed for IDC + DCIS was limited to patients with invasive tumor size < 4 cm or with node negative disease. A greater improvement in OS was observed for tumors containing ≥25% DCIS component. We also found IDC + DCIS to be associated with lower T/N stage, low/intermediate grade, ER/PR positivity, and receipt of mastectomy. Thus, the presence of a DCIS component in patients with IDC is associated with favorable clinical characteristics and independently predicts improved OS. IDC + DCIS could be a useful prognostic factor for patients with breast cancer, particularly if treatment de-escalation is being considered for small or node negative tumors.

Incidence of radiographically occult nodal metastases in HPV+ oropharyngeal carcinoma: Implications for reducing elective nodal coverage.

PURPOSE: Initial deescalation studies for human papilloma virus (HPV)-positive driven oropharyngeal squamous cell carcinomas (HPV+ OPSCC) altered radiation therapy dose or the systemic agent used. Newer trials examine the disease control achieved with a reduced elective nodal field. We examined patterns of nodal involvement in patients with HPV+ OPSCC with a focus on implications for radiation field design for treatment deescalation. METHODS AND MATERIALS: Records of patients with HPV+ OPSCC with preoperative imaging (computed tomography or fludeoxyglucose positron emission tomography/computed tomography) who underwent neck dissection without neoadjuvant therapy from 2010 to 2017 were retrospectively reviewed. The number and location of clinically positive lymph nodes on preoperative imaging were compared with those documented on pathology. These data were then used to establish the probability of missing nodal disease in 3 modified radiation field designs. RESULTS: One hundred patients were included. The median time between imaging and surgery was 22 days. The most common clinical N stage was cN2a (35%), whereas the most common pathologic N stage was pN2b (45%). The median number of radiographically and pathologically involved nodes was 1 (range, 0-6) and 2 (range, 0-11), respectively. Forty-three percent of patients had more pathologically involved nodes than predicted on imaging, whereas 21% had pathologic involvement at an additional nodal level not predicted on imaging. Of the 21 patients with additional pathologically involved nodal levels, 14 had involvement of a directly adjacent station, 4 were patients with a cN0 hemineck with pathologically positive level II disease, and 3 had pathologic involvement of level 2 echelons removed from that predicted on imaging. CONCLUSION: Our study suggests that radiation fields encompassing only clinically involved nodes or levels has an unacceptably high likelihood of missing subclinical disease. Alternatively, treating the first uninvolved echelon nodes in addition would cover pathologic sites of disease in 97% of patients. This approach merits further study in prospective trials.

Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma.

BACKGROUND: The 8th edition American Joint Committee on Cancer staging system for resected HPV-positive oropharynx carcinoma (HPV+ OPC) highlights high node number as a critical determinant of survival. We sought to characterize outcomes and patterns of failure in patients with high pathologically involved node number oropharynx cancer. METHODS: We retrospectively identified 116 HPV+ OPC patients sequentially treated with neck dissection and either resection or intraoperative brachytherapy of the primary tumor between 2010 and 2016. External beam radiation was given based on the pathologic findings. Cox proportional hazards regression was used for multivariate analysis. RESULTS: With a median follow-up of 27 months, the 3-year overall survival and progression free survival (PFS) were 89% and 81%, respectively. On multivariate analysis, ≥5 involved lymph nodes was significantly associated with worse PFS (hazard ratio 4.3, 95% confidence interval (CI) 1.5-12.0, P = 0.001). Rates of 3-year locoregional recurrence (LRR) in patients with ≤4 vs ≥5 were 6% and 22% (log-rank P = 0.12). Rates of 3-year distant metastases (DM) were 12% and 53% between ≤4 and ≥5 (log-rank P < 0.001). CONCLUSION: Our findings confirm that patients with 5 or more involved lymph nodes appear to have substantially worsened rates of disease recurrence. While these patients appear to be at high risk of both LRR and DM, the predominant mechanism of failure is distant, and the rate of DM in this group was over 50%. Dedicated clinical trials in this patient population are warranted with a focus on mitigating the high DM rate.

Upfront surgery versus definitive chemoradiotherapy in patients with human Papillomavirus-associated oropharyngeal squamous cell cancer.

OBJECTIVES: Currently, human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-A OPC) is managed with either primary surgery or definitive chemoradiotherapy (CRT), despite the lack of supporting randomized prospective data. We therefore assessed the outcomes of each treatment strategy using the National Cancer Database (NCDB). METHODS: The NCDB was used to identify patients diagnosed with cT1 N2a-2b or cT2 N1-2b HPV-A OPC from 2010 to 2013 who underwent treatment with primary surgery or CRT. Demographic and clinicopathologic predictors of treatment were analyzed by the chi-square test and logistic regression. Overall survival (OS) was evaluated using multivariable Cox proportional hazard regression, Kaplan-Meier, log-rank test, and propensity score-matched analysis. RESULTS: We identified 3063 patients; 1576 (51.5%) received CRT and 1487 (48.5%) underwent primary surgery. Median follow up was 32 months. 972 (65.4%) surgical patients received adjuvant CRT. On multivariable Cox regression, 3-year OS was comparable between surgery and CRT (hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.83-1.41, P = 0.58). Inferior OS was significantly associated with increasing clinical T and N stage, older age, and non-private insurance. Propensity score-matching yielded a 2526 patient cohort and redemonstrated similar OS (HR, 1.09; 95% CI 0.81-1.47; P = 0.55). Comparable outcomes persisted in a subset analysis of patients with margin-negative resection, with 3-year OS 90.8% in CRT patients vs. 93.6% in surgery patients (log-rank P = 0.27). CONCLUSIONS: Upfront surgery and CRT yielded comparable 3-year OS outcomes in this cohort. In this national sample, 65.4% of surgical patients received trimodal therapy with adjuvant CRT, highlighting the need for improved patient selection for primary surgery.

Pretreatment Identification of Head and Neck Cancer Nodal Metastasis and Extranodal Extension Using Deep Learning Neural Networks.

Identification of nodal metastasis and tumor extranodal extension (ENE) is crucial for head and neck cancer management, but currently only can be diagnosed via postoperative pathology. Pretreatment, radiographic identification of ENE, in particular, has proven extremely difficult for clinicians, but would be greatly influential in guiding patient management. Here, we show that a deep learning convolutional neural network can be trained to identify nodal metastasis and ENE with excellent performance that surpasses what human clinicians have historically achieved. We trained a 3-dimensional convolutional neural network using a dataset of 2,875 CT-segmented lymph node samples with correlating pathology labels, cross-validated and fine-tuned on 124 samples, and conducted testing on a blinded test set of 131 samples. On the blinded test set, the model predicted ENE and nodal metastasis each with area under the receiver operating characteristic curve (AUC) of 0.91 (95%CI: 0.85-0.97). The model has the potential for use as a clinical decision-making tool to help guide head and neck cancer patient management.

Brachytherapy Boost Utilization and Survival in Unfavorable-risk Prostate Cancer.

BACKGROUND: There are limited comparative survival data for prostate cancer (PCa) patients managed with a low-dose rate brachytherapy (LDR-B) boost and dose-escalated external-beam radiotherapy (DE-EBRT) alone. OBJECTIVE: To compare overall survival (OS) for men with unfavorable PCa between LDR-B and DE-EBRT groups. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base, we identified men with unfavorable PCa treated between 2004 and 2012 with androgen suppression (AS) and either EBRT followed by LDR-B or DE-EBRT (75.6-86.4Gy). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Treatment selection was evaluated using logistic regression and annual percentage proportions. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards, and propensity score matching. RESULTS AND LIMITATION: We identified 25038 men between 2004 and 2012, during which LDR-B boost utilization decreased from 29% to 14%. LDR-B was associated with better OS on univariate (7-yr OS: 82% vs 73%; p<0.001) and multivariate analyses (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.64-0.77). Propensity score matching verified an OS benefit associated with LDR-B boost (HR 0.74, 95% CI 0.66-0.89). The OS benefit of LDR-B boost persisted when limited to men aged <60 yr with no comorbidities. On subset analysis, there was no interaction between treatment and age, risk group, or radiation dose. Limitations include the retrospective design, nonrandomized selection bias, and the absence of treatment toxicity, hormone duration, and cancer-specific outcomes. CONCLUSIONS: Between 2004 and 2012, LDR-B boost utilization declined and was associated with better OS compared to DE-EBRT alone. LDR-B boost is probably the ideal treatment option for men with unfavorable PCa, pending long-term results of randomized trials. PATIENT SUMMARY: We compared radiotherapy utilization and survival for prostate cancer (PCa) patients using a national database. We found that low-dose rate brachytherapy (LDR-B) boost, a method being used less frequently, was associated with better overall survival when compared to dose-escalated external-beam radiotherapy alone for men with unfavorable PCa. Randomized trials are needed to confirm that LDR-B boost is the ideal treatment.

Comparison of Survival Outcomes Among Human Papillomavirus-Negative cT1-2 N1-2b Patients With Oropharyngeal Squamous Cell Cancer Treated With Upfront Surgery vs Definitive Chemoradiation Therapy: An Observational Study.

IMPORTANCE: Human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) has shown resistance to conventional concurrent chemoradiation (CRT) therapy and carries a relatively poor prognosis in comparison with HPV-positive disease, with decreased locoregional control and overall survival (OS). In the present analysis, we examine whether upfront surgical resection improves overall survival in a large national sample. OBJECTIVE: To compare survival outcomes among patients with newly diagnosed cT1-2 N1-2b HPV-negative OPSCC when treated with primary surgical resection vs CRT. DESIGN, SETTING, AND PARTICIPANTS: This was an observational study of factors associated with primary treatment modality were identified using multivariable logistic regression. Overall survival was compared using Kaplan-Meier analysis with log-rank tests, multivariable Cox regression, and propensity score matching. Statistical tests were 2-sided. Patients newly diagnosed as having cT1-2 N1-2b pathologically confirmed HPV-negative OPSCC in 2010 to 2012 were identified using the National Cancer Data Base, which includes more than 70% of patients newly diagnosed as having cancer in the United States. EXPOSURES: Primary surgical resection vs definitive CRT. MAIN OUTCOMES AND MEASURES: Overall survival. RESULTS: We identified 1044 patients, among whom 460 (44.1%) received upfront surgery and 584 (55.9%) received CRT. Median age was 59 years (range, 25-90 years); 812 patients were male (77.8%), 232 were female (22.2%). Median follow-up was 30 months. Approximately 59% of surgical patients received adjuvant CRT. On multivariable Cox regression, upfront surgery was not associated with increased OS when compared with CRT (adjusted hazard ratio [HR], 1.01; 95% CI, 0.74-1.39; P = .93). Propensity score-matching identified a cohort of 822 patients and redemonstrated equivalent OS (HR, 1.14; 95% CI, 0.81-1.62; P = .46). Lack of OS benefit with upfront surgery persisted in a subset analysis of patients with margin-negative resection (HR, 0.97; 95% CI, 0.66-1.45; P = .88). CONCLUSIONS AND RELEVANCE: In this observational study, OS was similar for patients with HPV-negative OPSCC when treated with primary surgery vs CRT. Most surgical patients received trimodal therapy with adjuvant CRT. Our data may have implications for future research focusing on optimal patient selection for surgery.

The risk of level IB nodal involvement in oropharynx cancer: Guidance for submandibular gland sparing irradiation.

PURPOSE: Xerostomia remains a common side effect of head and neck irradiation. Conflicting data exist regarding the likelihood of level IB involvement for patients with oropharyngeal squamous cell cancer (OPSCC), and data are limited on this risk in patients with human papillomavirus-positive disease. This study examined surgically treated OPSCC to determine the risk of pathologic level IB nodal involvement and to identify a cohort of patients in whom ipsilateral level IB radiation therapy may be safely omitted. METHODS AND MATERIALS: A total of 102 submandibular nodal dissections were identified (92 ipsilateral and 10 contralateral) in 92 patients from 2010 to 2016 in those undergoing primary surgical treatment and dissection of ipsilateral level IB lymph nodes. Radiographically positive cases were excluded. Retrospective chart review was used for data collection, and the rate of pathologic level IB involvement was determined. RESULTS: The ipsilateral level IB nodal station had negative imaging and pathologically positive nodes at rates of 4.3% in OPSCC and 5.3% in human papillomavirus-positive OPSCC. Positive node burden in the ipsilateral neck at stations other than IB appeared to correlate with the risk of pathologic positive IB (pIB+) nodes: 50% of pathologically IB-negative patients had 2 or more positive nodes versus 75% of pIB+ patients who had 4 or more positive nodes. CONCLUSIONS: Our data indicate a low risk of pathologic level IB involvement in early-stage OPSCC. High positive node burden in stations near level IB may be associated with a higher chance of pathologic level IB involvement.

Adjuvant chemotherapy and overall survival in adult medulloblastoma.

Background: Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Methods: Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Results: Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). Conclusions: This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI.

Treatment de-intensification strategies for head and neck cancer.

Increasingly, squamous cell carcinoma of the oropharynx (OPSCC) is attributable to transformation resulting from high-risk human papillomavirus (HPV) infection. Such cancers are significantly more responsive to treatment than traditional tobacco- and alcohol-associated squamous cell cancers of the head and neck. Conventional management with definitive chemoradiation, surgery and adjuvant radiation, or radiation given with altered fractionation schemes, while effective, incurs long-term morbidity that escalates with treatment intensity and significantly impairs quality of life. Recent trials have suggested that less intensive treatment regimens may achieve similar efficacy with decreased toxicity. In this article, we review the primary strategies used for de-escalation of treatment, which include the reduction of radiation dose, substitution and/or elimination of concurrent radiosensitising chemotherapy, and the use of minimally invasive surgery. We discuss the rationale behind these approaches and the preliminary data demonstrating the success of de-escalation, as well as potential considerations raised by treatment de-intensification in HPV-associated OPSCC.