Adjuvant chemotherapy versus observation following neoadjuvant therapy and surgery for resectable stage I-II pancreatic cancer.

Background: Neoadjuvant therapy (NT), either with systemic treatment alone or in combination with radiation, is often utilized in the management of pancreatic adenocarcinoma to increase the likelihood of margin-negative resection. Following NT and resection, additional adjuvant chemotherapy (AC) can be considered for select patients and has been shown to improve overall survival (OS). This National Cancer Data Base (NCDB) analysis was performed to evaluate the outcomes of AC versus observation for resected pancreatic adenocarcinoma treated with NT. Methods: The NCDB was queried for primary stage I-II cT1-3N0-1M0 resected pancreatic adenocarcinoma treated with NT (2004-2015). Baseline patient, tumor, and treatment characteristics were extracted. The primary endpoint was OS. With a 6-month conditional landmark, Kaplan-Meier analysis, multivariable Cox proportional hazards method, 1:1 propensity score matching were used to analyze the data. Results: A total of 1737 eligible patients were identified, of which 1247 underwent postoperative observation compared to 490 with AC. The overall median follow-up was 34.7 months. The addition of AC showed improved survival on the multivariate analysis (HR 0.78, p<0.001). Of 490 propensity-matched pairs, all variables were well balanced, including age (p=0.61), Charlson-Deyo comorbidity score (p=0.80), ypT stage (p=0.93), ypN stage (p=0.83), surgical margin (p=0.83), duration of postoperative inpatient admission (p=0.96), and 30-day unplanned readmission after resection (p=0.34). AC remained statistically significant for improved OS, with median OS of 26.3 months vs 22.3 months and 2-year OS of 63.9% vs 52.9% for the observation cohort (p<0.001). Treatment interaction analysis showed OS benefit of AC for patients with smaller tumors (HR 0.67, p<0.001 for <3.1 cm vs HR 0.93, p=0.48 for ≥3.1 cm). Conclusion: Using propensity score matched analysis, our findings suggest a survival benefit for adjuvant chemotherapy compared to observation following NT and surgery for resectable pancreatic adenocarcinoma, especially in patients with smaller tumors. Prospective studies are needed to identify subset of patients that would benefit from adjuvant chemotherapy.

Association of survival with stereotactic body radiation therapy following induction chemotherapy for unresected locally advanced pancreatic cancer.

Background: Induction chemotherapy (iC) followed by concurrent chemoradiation has been shown to improve overall survival (OS) for locally advanced pancreatic cancer (LAPC). However, the survival benefit of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT) following iC remains unclear. Methods: The National Cancer Database (NCDB) was queried for primary stage III, cT4N0-1M0 LAPC (2004-2015). Kaplan-Meier analysis, Cox proportional hazards method, and propensity score matching were used. Results: Among 872 patients, 738 patients underwent CFRT and 134 patients received SBRT. Median follow-up was 24.3 months and 22.9 months for the CFRT and SBRT cohorts, respectively. The use of SBRT showed improved survival in both the multivariate analysis (HR 0.78, p=0.025) and 120 propensity-matched pairs (median OS 18.1 vs 15.9 months, p=0.004) compared to the CFRT. Conclusion: This NCDB analysis suggests survival benefit with the use of SBRT versus CFRT following iC for the LAPC.

Intravenous fluids for pain management in head and neck cancer patients undergoing chemoradiation.

BACKGROUND: Pain due to oral mucositis affects the majority of patients receiving chemoradiation (CRT) for head and neck cancer (HNC), and often results in dehydration. Anecdotally, intravenous (IV) fluids administered during treatment for the resultant dehydration was found to alleviate this pain. The purpose of this retrospective study was to evaluate the effectiveness of IV fluids as a method pain management in this patient population. METHODS: Patients with oral mucositis pain, secondary to CRT for HNC, were given IV fluids according to standard clinic protocol. Patients were evaluated using orthostatic vital signs and prospectively surveyed pre- and post-IV fluid administration, which included the Visual Analog Scale (VAS) for pain. Difference in pain pre- and post-IV fluid administration was evaluated using a two-tailed paired Student's t-test. RESULTS: Twenty-four patients with a total of 31 fluid administrations was available for analysis. Twenty-three patients were receiving or had recently completed CRT. One patient was receiving radiation alone. Six instances of fluid administration were excluded due to: refusal to complete the survey, concurrent pulmonary embolism, concurrent pain medication, and drug seeking behavior. Average pain score decreased from 6.5 [standard deviation (SD) 2.1] prior to IV fluids to 4.0 (SD 2.4) following fluid administration (P<0.001). CONCLUSIONS: To our knowledge, this is the first report directly correlating IV fluid administration with pain relief, even in the absence of orthostasis. Our findings indicate that in patients undergoing CRT for HNC, the use of IV fluids alone was effective in acutely and significantly reducing pain secondary to oral mucositis.

Matched pair analysis for comparison of survival outcome of alternative regimens to standard three-weekly cisplatin-based concurrent chemoradiation of head and neck cancer.

BACKGROUND: To compare head and neck cancer (HNC) patients treated with three-weekly versus weekly cisplatin-based or other chemotherapy-based concurrent chemoradiation (CRT) and CRT with versus without induction chemotherapy (ICT) to investigate differences in overall survival (OS) and cancer-specific survival (CSS). METHODS: HNC patients treated with definitive or adjuvant CRT at Roswell Park Comprehensive Cancer Center between 2003 and 2017 were retrospectively reviewed. Propensity score matching was performed to obtain three sets of balanced matched pairs: three-weekly and weekly cisplatin CRT, three weekly and non-cisplatin CRT, CRT with and without ICT. Multivariate Cox regression and Kaplan-Meier analyses were used to estimate and compare survival outcomes. RESULTS: A total of 623 patients received either definitive (81%) or post-operative (19%) RT. Of these, 283 patients concurrently received three-weekly cisplatin (45%); 189 patients (30%) received weekly cisplatin; 151 patients (24%) received non-cisplatin regimen. Median follow-up was 55.4 months (interquartile range, 38.0-88.7). Patients who received CRT alone and those who received ICT and CRT had no difference in 5-year OS (51.5% and 41.0% respectively, P=0.53) and CSS (64.9% and 49.7% respectively, P=0.21). Compared to patients who received three-weekly cisplatin, patients who received weekly cisplatin had no difference in 5-year OS (59.3% vs. 54.1%, P=0.35) and CSS (70.3% vs. 62.4%, P=0.09); patients who received non-cisplatin CRT also had no difference in 5-year OS (54.5% vs. 58.3%, P=0.51) and CSS (67.5% vs. 64.7%, P=0.45). CONCLUSIONS: No significant difference in OS and CSS was observed in any of the three pairs of CRT regimens. ICT prior to CRT did not improve survival of CRT alone. Non-cisplatin and weekly cisplatin regimens did not prove to be inferior to the standard three-weekly cisplatin.

Matched pair analysis to evaluate weight loss during radiation therapy for head and neck cancer as a prognostic factor for survival.

BACKGROUND: One frequent consequence of radiation therapy (RT) for head and neck cancer (HNC) is weight loss (WL). HNC patients reportedly lose about 9% of their weight during treatment, regardless of pre-treatment WL and nutritional support. We investigated whether high WL during RT has an association with overall (OS) and cancer-specific survival (CSS). METHODS: We retrospectively reviewed weight during RT in HNC patients treated at Roswell Park Comprehensive Cancer Center between 2003 and 2017. High WL was defined as greater than or equal to the median WL. Logistic regression analysis was performed to identify predictors for WL during RT. Multivariate Cox regression and Kaplan-Meier analyses were used to estimate survival outcomes. Propensity score matching was performed to obtain balanced matched-pairs and compare survival outcomes. RESULTS: A total of 843 patients received either definitive (71%) or post-operative (29%) RT. Median follow-up was 53.6 months [interquartile range (IQR) 35.7-88.9]. Median WL was 5.8% (IQR 0.24-10.6) from baseline weight. Patients with high WL had better OS [hazard ratio (HR) 0.75, 95% confidence interval (CI), 0.61-0.93, P=0.01] and CSS (HR 0.71, 95% CI, 0.55-0.93, P=0.01). 258 matched-pairs were analyzed. Median follow-up was 54.8 months (IQR 35.8-90.4). Median OS was 39.2 months (IQR 21.4-75.7) for high WL versus 36.7 months (IQR 14.6-61.7) for low WL cohorts (P=0.047). CONCLUSIONS: Different from previous reports, this study shows that patients with less WL have worse OS. WL during RT may not be a reliable marker for worse prognosis. A better way to evaluate malnutrition in patients undergoing RT is warranted.

Association of Nonsteroidal Anti-inflammatory Drug Use With Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Chemoradiation Therapy.

Importance: Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are commonly prescribed medications with anti-inflammatory and antiplatelet properties used long term to decrease the risk of cardiovascular events. A recent study showed that aspirin was associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) who were treated with surgery. Objective: To examine whether use of NSAIDs during definitive chemoradiation therapy (CRT) was associated with improved outcomes in patients with HNSCC. Design, Setting, and Participants: This cohort study analyzed patients with HNSCC who were treated with CRT at a single institution between January 1, 2005, and August 1, 2017. Patient and tumor characteristics included age, race/ethnicity, smoking status, alcohol use, comorbidities (respiratory, cardiovascular, immune, renal, endocrine), disease stage, human papillomavirus status, and treatment duration. Data were analyzed from May 1, 2019, to March 17, 2020. Exposures: Patients were dichotomized by NSAID use during treatment. Main Outcomes and Measures: The association of NSAID use with patterns of failure, disease-specific survival (DSS), and overall survival (OS) was examined using multivariate Cox proportional hazard regression models. Survival estimates for OS and DSS were generated using Kaplan-Meier survival curves. Results: A total of 460 patients (median [interquartile range] age, 60 [53.9-65.6] years; 377 [82.0%] men) were included in the analysis. Among these patients, 201 (43.7%) were taking NSAIDs during treatment. On univariate analysis, NSAID use (hazard ratio [HR], 0.63; 95% CI, 0.43-0.92; P = .02) was associated with better OS. On Cox regression analysis, after backward selection adjustment for potentially confounding factors (age, smoking status, primary tumor site, human papillomavirus status, diabetes, stroke, hyperlipidemia), NSAID use remained significantly associated with better OS (HR, 0.59; 95% CI, 0.38-0.90; P = .02). NSAID use was associated with significantly better OS at 5 years compared with patients who did not take concurrent NSAIDs (63.6% [56 of 88 patients]; 95% CI, 58%-73% vs 56.1% [83 of 148 patients]; 95% CI, 50%-63%; P = .03). NSAID use was not associated with better DSS in univariate (HR, 0.82; 95% CI, 0.48-1.41; P = .47) or multivariate (HR, 0.98; 95% CI, 0.57-1.70; P = .44) analysis. NSAID use was not associated with better response to treatment (HR, 1.44; 95% CI, 0.91-2.27; P = .12) or distant failure (HR, 1.12; 95% CI, 0.68-1.84; P = .65). Change in local control with NSAID use was not statistically significant (HR, 0.59; 95% CI, 0.31-1.10; P = .10). Conclusions and Relevance: This cohort study suggests a possible OS advantage for patients taking NSAIDs during chemoradiation for HNSCC. Further studies examining this association are warranted.

Matched pair analysis to evaluate the impact of hospitalization during radiation therapy as an early marker of survival in head and neck cancer patients.

BACKGROUND: Complications from radiotherapy (RT) alone or combined with surgery and/or chemotherapy for head and neck cancer (HNC) sometimes necessitate hospitalization. Our aim was to evaluate the frequency, cause, and survival outcomes associated with hospitalizations in patients undergoing RT for HNC. PATIENTS AND METHODS: Using a retrospective single-institution database, we reviewed hospitalization records of HNC patients treated at Roswell Park Comprehensive Cancer Center with definitive or post-operative RT between 2003 and 2017. Patients who were admitted during treatment and within 90-days post-RT were identified. Multivariate analyses, Kaplan-Meier statistics, and analysis on propensity score matching were performed to obtain matched-pair, after matching baseline characteristics, such as age, gender, smoking, tumor staging, p16 status, and treatments received. RESULTS: 839 patients were eligible for analysis. Median follow-up was 34.8 months (Interquartile range [IQR] 15.6-64.8). 595 (71%) received definitive RT and 244 (29%) received adjuvant RT. Chemotherapy was used in 671 patients (80%). 171 patients (20%) had at least one hospitalization. Dehydration (40%) and fever (29%) were the most frequent causes of admission. Hospitalized patients had significantly worse overall survival (OS) (Hazards ratio [HR] 1.61, 95% CI 1.26-2.07, p < 0.001) and cancer-specific survival (CSS) (HR 1.45, 95% CI 1.07-1.95, p = 0.02). 163 matched pairs had median follow-up of 58.6 months (IQR 37.6-85.0). Median OS was 34.5 months (IQR 13.3-58.0) for hospitalized versus 44.2 months (IQR 20.3-78.7) for non-hospitalized patients (p = 0.01). CONCLUSION: This study reveals significantly worse OS and CSS for patients hospitalized during RT for HNC. Hospitalization may be an early marker for worse survival.

Two- Versus Four-Times Weekly Acupuncture-Like Transcutaneous Electrical Nerve Stimulation for Treatment of Radiation-Induced Xerostomia: A Pilot Study.

Background: Xerostomia occurs in the majority of patients undergoing chemoradiation therapy for head and neck cancer (HNC). Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) treatment has been studied as an encouraging modality to improve salivary function and related symptoms. The purpose of this study was to compare ALTENS treatment by using a four-times weekly schedule for 6 weeks versus a twice-weekly schedule for 12 weeks with a validated xerostomia scale at 15 months from the start of ALTENS treatment. Materials and Methods: This single-center randomized study was conducted in 30 patients treated with radiotherapy with or without chemotherapy for HNC between 2014 and 2017, who had at least grade 1 or 2 symptomatic dry mouth (xerostomia) according to CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0). These patients were randomly assigned to receive ALTENS four-times weekly for 6 weeks or two-times weekly for 12 weeks. The University of Michigan 15-item Xerostomia-related Quality of Life Scale (XeQoLS) was administered at 6, 9, 15, and 21 months from the start of ALTENS treatment. A random-effects generalized linear model was used to model the overall XeQoLS score at the 15-month endpoint; adjusted for a random time effect, a fixed treatment arm, and interaction of time and treatment. Comparison between arms was based on a 0.05 nominal significance level. Results: XeQoLS decreased for all patients (although not statistically for each arm) from a mean of 22 and 21 at baseline (in the four times per week and twice weekly arms) to 12 in both arms at 15 months, with no difference between arms (p = 0.68). There were no attributable grade 1-3 adverse events. Arms were balanced for age, gender, race, and baseline xerostomia. Conclusions: This study demonstrates that both ALTENS regimens are safe, well tolerated, and appear to be equally effective. We now routinely make ALTENS units available for home use.

A single-institution, randomized, pilot study evaluating the efficacy of gabapentin and methadone for patients undergoing chemoradiation for head and neck squamous cell cancer.

BACKGROUND: The objective of the current study was to compare the safety and efficacy between 2 analgesic regimens for patients with head and neck cancer (HNC) undergoing definitive chemoradiation (CRT). METHODS: The current study was a prospective, single-institution, 2-arm, randomized pilot study. Patients with American Joint Committee on Cancer seventh edition stage II to stage IV squamous cell carcinoma of the head and neck who were undergoing CRT were randomized to either arm 1, which entailed high-dose gabapentin (2700 mg daily) with the institutional standard of care (hydrocodone and/or acetaminophen progressing to fentanyl as needed), or arm 2, which comprised low-dose gabapentin (900 mg daily) with methadone. The primary endpoints were safety and toxicity. Secondary endpoints were pain, opioid requirement, and quality of life (QOL). Differences between the treatment arms at multiple time points were compared using a generalized linear mixed regression model with Sidak correction. RESULTS: A total of 60 patients (31 in arm 1 and 29 in arm 2) were enrolled from April 2015 to August 2017. There was no difference between the treatment arms with regard to adverse events or serious adverse events. Pain was not found to be different between the treatment arms. More patients in arm 1 did not require an opioid during treatment (42% vs 7%; P = .002). Patients in arm 2 experienced significantly better QOL outcomes across multiple domains, including overall health (P = .05), physical functioning (P = .04), role functioning (P = .01), and social functioning (P = .01). CONCLUSIONS: High-dose prophylactic gabapentin increased the percentage of patients who required no opioid during treatment. Methadone may improve QOL compared with a regimen of short-acting opioids and fentanyl. However, pain was found to significantly worsen throughout treatment regardless of treatment arm, necessitating further studies to identify a more optimal regimen.

Association of Timing of Adjuvant Therapy With Survival in Patients With Resected Stage I to II Pancreatic Cancer.

Importance: Surgery followed by adjuvant chemotherapy or chemoradiation is widely used to treat resectable pancreatic cancer. Although studies suggest initiation of adjuvant therapy within 12 weeks of surgery, there is no clear time interval associated with better survival. Objective: To evaluate the ideal timing of adjuvant therapy for patients with stage I to II resected pancreatic cancer. Design, Setting, and Participants: This cohort study included 7548 patients with stage I to II resected pancreatic cancer (5453 with adjuvant therapy; 2095 without adjuvant therapy) from the National Cancer Database from 2004 to 2015. Data were collected from January 2014 to December 2015 and analyzed from December 2018 to May 2019. Exposures: Adjuvant chemotherapy or chemoradiation at various time intervals. Main Outcomes and Measures: Overall survival (OS). Results: A total of 7548 patients (3770 male [49.9%]; median [interquartile range] age, 67 [59-74] years) were identified from the National Cancer Database. Among 5453 patients with adjuvant therapy, a Cox model with restricted cubic splines identified the lowest mortality risk when adjuvant therapy was started 28 to 59 days after surgery. Patients were divided into early (n = 269, adjuvant therapy initiated within <28 days), reference (n = 3048, adjuvant therapy initiated within 28-59 days), and late (n = 2136, adjuvant therapy initiated after >59 days) interval cohorts. Median (interquartile range) overall follow-up was 38.6 (24.6-62.0) months. Compared with the reference interval cohort on multivariable analysis, both the early cohort (hazard ratio, 1.17; 95% CI, 1.02-1.35; P = .03) and the late cohort (hazard ratio, 1.09; 95% CI, 1.02-1.17; P = .008) were associated with worse mortality. Similarly, the reference interval cohort had improved OS compared with the early cohort in 268 propensity-matched pairs (2-year OS, 52.5% [95% CI, 46.7%-59.0%] vs 45.1% [95% CI, 39.5%-51.6%]; P = .02) and compared with the late cohort in 2042 propensity-matched pairs (2-year OS, 51.3% [95% CI, 49.1%-53.6%] vs 45.4% [95% CI, 43.3%-47.7%]; P = .01). Patients who received adjuvant therapy more than 12 weeks after surgery (n = 683) had improved OS compared with surgery alone in both multivariable analysis (hazard ratio, 0.75; 95% CI, 0.66-0.85; P < .001) and 655 propensity-matched pairs (2-year OS, 47.2% [95% CI, 43.5%-51.3%] vs 38.0% [95% CI, 34.4%-42.0%]; P < .001). Conclusions and Relevance: Patients with stage I to II pancreatic cancer who commenced adjuvant therapy within 28 to 59 days after primary surgical resection had improved survival outcomes compared with those with adjuvant therapy before 28 days or after 59 days. Patients who recovered slowly from surgery still benefited from delayed adjuvant therapy initiated more than 12 weeks after surgery compared with patients who underwent surgery only.

One Versus Three Fractions of Stereotactic Body Radiation Therapy for Peripheral Stage I to II Non-Small Cell Lung Cancer: A Randomized, Multi-Institution, Phase 2 Trial.

PURPOSE: Stereotactic body radiation therapy for early stage non-small cell lung cancer is a standard of care for medically inoperable patients. Our aim was to compare Common Terminology Criteria for Adverse Events thoracic grade 3 or higher adverse events (AEs) of 30 Gy in 1 fraction (arm 1) versus 60 Gy in 3 fractions (arm 2). METHODS AND MATERIALS: This was a randomized multi-institutional, phase 2, 2-arm clinical trial. Medically inoperable patients with biopsy-proven peripheral T1/T2N0M0 non-small cell lung cancer were enrolled. Patients were randomized to arm 1 or arm 2 and stratified by performance status. The primary endpoint was Common Terminology Criteria for Adverse Events thoracic grade 3 or higher AEs. Secondary endpoints were local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life. RESULTS: Between September 2008 and April 2015, 98 patients were randomized. Median follow-up was 53.8 months. Ten patients were lost to follow-up, 1 in arm 1 and 9 in arm 2. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no grade 4 or 5 AEs. There were no differences in LC, PFS, or OS (P = .68, .86, and .94, respectively). Arm 1 reported better social functioning (P = .006) with less dyspnea (P = .016) in follow-up at 6 months. CONCLUSIONS: This randomized phase 2 study demonstrated that 30 Gy in 1 fraction was equivalent to 60 Gy in 3 fractions in terms of toxicity, LC, PFS, and OS. Quality of life measures of social functioning and dyspnea favored single-fraction SBRT.

Duration of chemotherapy prior to chemoradiation affects survival outcomes for resected stage I-II or unresected stage III pancreatic cancer.

BACKGROUND: For resected early stage pancreatic cancer, RTOG 9704 evaluated the outcome of 3 weeks of postoperative chemotherapy (C) followed by chemoradiation (CRT) and further C. For unresectable locally advanced pancreatic cancer, a recent literature review of prospective studies showed that the duration of induction C prior to CRT can impact survival. However, the ideal duration of C prior to CRT remains unclear for these patient cohorts. This National Cancer Database (NCDB) study was performed to compare the outcome of various durations of C prior to CRT. METHODS: The NCDB was queried for resected primary stage I-II, cT1-3N0-1M0, and unresected stage III, cT4N0-1M0 pancreatic adenocarcinoma treated with C + CRT (2004-2015). Cohorts I-II and III included stage I-II and stage III cases, respectively. Patients were stratified by short (short C) and long duration (long C) of chemotherapy based on their median durations. Baseline patient, tumor, and treatment characteristics were examined. The primary endpoint was overall survival (OS). Kaplan-Meier analysis, multivariable Cox proportional hazards method, and propensity score matching were used. RESULTS: Among 1577 patients, cohort I-II had 839 patients and cohort III had 738 patients. The longer duration of chemotherapy prior to CRT showed improved OS in the multivariate analysis in both cohort I-II (hazards ratio [HR] 0.72, P < 0.001) and cohort III (HR 0.83, P = 0.03). Using 1:1 propensity score matching, 610 patients for cohort I-II and 542 patients for cohort III were matched. After matching, long C remained statistically significant for improved OS compared with short C in both cohort I-II (median OS 26.1 vs 21.9 months; P = 0.003) and cohort III (median OS 16.7 vs 14.2; P = 0.02). CONCLUSION: Our NCDB study using propensity score-matched analysis showed a survival benefit for using the longer duration of chemotherapy compared to the shorter duration for both resected stage I-II and unresected stage III pancreatic cancer.

The Extent of Neck Dissection Among Patients Who Receive Adjuvant Radiotherapy for HNSCC and Its Effect on Disease-Specific and Overall Survival.

The study objective was to assess if the extent of neck dissection among patients who receive adjuvant radiotherapy affects regional recurrence and survival. This was a retrospective study of patients who had clinical metastatic mucosal primary squamous cell carcinoma (SCC) to cervical lymph nodes done at Roswell Park Comprehensive Cancer Center, Buffalo, New York from 2004 to 2015. Patients with previous radiotherapy and/or chemotherapy were excluded. All patients had surgery to the primary tumor and the neck followed by adjuvant (chemo) radiation. Patients have been divided into 2 groups according to type of neck dissection as either selective neck dissection (SND) or comprehensive neck dissection (CND). The extent of neck dissection was determined by surgeon preference. All patients received postoperative radiotherapy to the primary tumor bed and to the neck with or without chemotherapy. Main outcomes were measured in regional recurrence and overall survival. In our study, 74 patients were included. Among the 2 groups of patients, 3-year outcomes for regional recurrence occurred in 4 (7.1%) of 56 patients in the SND group and 2 (11.1%) of 18 patients in the CND group. Overall survival was 29 (51.8%) of 56 patients in the SND group and 11 (61.1%) of 18 patients in the CND group ( P = .497). Among patients who died in each cohort, disease-specific death was 20 (74.1%) of 27 patients in the SND group and 5 (71.4%) of 7 patients in the CND group ( P = .79).The overall and disease-specific survival differences between the SND and CND cohorts were not statistically significant. In conclusion, SND, combined with proper adjuvant treatment, achieved regional control and survival rates comparable to CND.

Adjuvant chemotherapy followed by concurrent chemoradiation is associated with improved survival for resected stage I-II pancreatic cancer.

BACKGROUND: This National Cancer Database (NCDB) analysis evaluates the clinical outcomes of postoperative chemotherapy followed by concurrent chemoradiation (C + CRT) compared to concurrent chemoradiation (CRT) alone or adjuvant chemotherapy alone (C) for resected pancreatic cancer. METHODS: The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected pancreatic adenocarcinoma treated with adjuvant C, CRT, or C + CRT (2004-2015). Patients treated with C + CRT were compared with those treated with C (cohort C) and CRT (cohort CRT). Baseline patient, tumor, and treatment characteristics were examined. Kaplan-Meier analysis, multivariable Cox proportional hazards method, forest plot, and propensity score matching were used. RESULTS: Among 5667 patients, median follow-up was 34.7, 45.2, and 39.7 months for the C, CRT, and C + CRT cohorts, respectively. By multivariable analysis for all patients, C and CRT had worse OS compared to C + CRT. Treatment interactions were seen among pathologically node-positive disease. C + CRT was favored in 1-3 and 4+ positive lymph node diseases when compared to C or CRT alone, but none of the treatment options were significantly favored in node negative disease. Using propensity score matching, 2152 patients for cohort C and 1774 patients for cohort CRT were matched. C + CRT remained significant for improved OS for both cohort C (median OS 23.3 vs 20.0 months) and cohort CRT (median OS 23.4 vs 20.8 months). CONCLUSION: This NCDB study using propensity score matched analysis suggests an OS benefit for C + CRT compared to C or CRT alone following surgical resection of pancreatic cancer, particularly for patients with pathologically positive lymph nodes.

Stereotactic body radiation therapy for non-small cell lung cancer: A review.

Stereotactic body radiation therapy (SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer (NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility, prescription dose and delivery, and follow up duration varied widely. Three-years overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Radiofrequency Ablation and Radiation Therapy Improve Local Control in Spinal Metastases Compared to Radiofrequency Ablation Alone.

PURPOSE:: The spinal column is the most common location for osseous metastases and is associated with pain and decreased quality of life. This study evaluated combined radiofrequency ablation (RFA) with radiation therapy (RT) compared to RFA alone for improving pain and local control. METHODS:: This was a single-institution retrospective review of patients who underwent RFA of spinal metastases between 2016 and 2017, with or without RT to the same vertebral level. Pain was measured with visual analog scale at initial presentation and at 3 and 12 weeks of follow-up. Local failure (LF), distant failure, and overall survival (OS) were compared and Kaplan-Meier statistics were calculated. RESULTS:: Twenty-six patients with 28 spinal metastases were treated with RFA. Ten patients with 11 metastases were treated with RFA + RT. More patients with lung primaries were treated with RFA alone and more patients with breast primaries were treated with combination RFA+RT. There was no significant difference in pain scores between groups ( P = .96). At a median follow-up of 8.2 months, LF was noted in 8 of 17 metastases treated with RFA alone compared to 1 of 11 metastases treated with RFA+RT ( P = .049). There was a significant benefit in time to LF favoring RFA+RT ( P = .02) and a significant benefit in OS ( P = .0045). CONCLUSION:: This study demonstrates a benefit in local control with RFA+RT versus RFA alone. Palliation of pain was effective using both regimens. This study was limited by a nearly unequal distribution of primary tumor histologies between groups. Literature regarding combined treatment of RFA and RT for spinal metastases is scarce and prospective protocols are warranted.

A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer.

BACKGROUND: Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. METHODS: Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. RESULTS: Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4-5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36-86) and 40% (90% CI 16-63), respectively. CONCLUSIONS: In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. TRIAL REGISTRATION: ClinicalTrials.gov identifying number NCT01781741 . Registered February 1, 2013.

Dose escalation of radiation therapy with or without induction chemotherapy for unresectable locally advanced pancreatic cancer.

BACKGROUND: Dose escalation of conventionally fractionated radiation therapy (CFRT) above 45-54 Gy has an unclear survival benefit. Prior National Cancer Database (NCDB) analyses have shown improved overall survival with induction chemotherapy (iC) prior to concurrent chemoradiation (CRT) in locally advanced pancreatic cancer. Our study compared dose-escalated CFRT with and without iC. METHODS: The NCDB was queried for primary stage III, cT4 N0-1 M0 LAPC treated with CRT with or without iC (2004-2015). CFRT was stratified by < 55 Gy and ≥ 55 Gy. Cohort iC + CRT and CRT included those with and without iC, respectively. The primary endpoint was overall survival (OS). Kaplan-Meier analysis, Cox proportional hazards method, and propensity score matching were used. RESULTS: Among 2029 patients, cohort iC + CRT had 738 patients (n = 601 for 45-55 Gy and n = 137 for ≥55 Gy) and cohort CRT had 1291 patients (n = 1066 for 45-55 Gy and n = 225 for ≥55 Gy). Median follow-up was 24.3 months and 24.6 months for cohorts iC + CRT and CRT, respectively. Dose escalation showed improved survival in the multivariable analysis in cohort iC + CRT (HR 0.77, p = 0.013) but not in cohort CRT (HR 0.91, p = 0.19). Using 2:1 propensity score matching, a total of 387 patients for cohort iC + CRT and 549 patients for cohort CRT were matched. After matching, dose escalation remained significant for improved overall survival in cohort iC + CRT (median OS 16.2 vs 15.2 months; 2-yr OS 33.4% vs 25.4%; p = 0.022) but not in cohort CRT (median OS 11.8 vs 10.6 months; 2-yr OS 13.3% vs 10.1%; p = 0.16). CONCLUSIONS: Patients with locally advanced pancreatic cancer who undergo iC have improved survival with radiation dose escalation above 55 Gy. For patients without iC, there is no clear association between radiation dose escalation and survival.

Comparison of Single- and Three-fraction Schedules of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non-Small-cell Lung Cancer.

BACKGROUND: To compare the clinical outcomes of patients with early-stage non-small-cell lung cancer (NSCLC) who had undergone either single-fraction (SF) or three-fraction (TF) stereotactic body radiation therapy (SBRT) at a single institution during over 8-year period. PATIENTS AND METHODS: Patients with peripherally located early-stage NSCLC who had undergone SBRT from February 2007 to November 2015 were included in the present study. SBRT was delivered without heterogeneity correction. Data were retrospectively reviewed and collected in an institutional review board-approved database. R software (version 3.3.2) was used for statistical analysis. RESULTS: Of 159 total lung tumors, 65 lesions received 30 Gy (median, 30 Gy) in 1 fraction, and 94 lesions received 48 to 60 Gy (median, 60 Gy) in 3 fractions. Patients with a Karnofsky performance status < 80 were more common in the SF-SBRT cohort (P = .050). After a median follow-up of 22.2 and 26.2 months for the SF-SBRT and TF-SBRT cohorts, respectively (P = .29), no statistically significant difference was found in overall survival (P = .86), progression-free survival (P = .95), local failure (P = .95), nodal failure (P = .91), and distant failure (P = .49) at 24 months. At 1 and 2 years, the overall survival rates were 86.1% and 63.2% for the SF-SBRT cohort and 80.8% and 61.6% for the TF-SBRT cohort, respectively. At 1 and 2 years, the local control rates were 95.1% and 87.8% for the SF-SBRT cohort and 92.7% and 86.2% for the TF-SBRT cohort, respectively. Both regimens were well tolerated. CONCLUSION: Despite more patients with poor performance status in the SF-SBRT cohort, the SF- and TF-SBRT regimens showed no differences in clinical outcomes. SF-SBRT is now our standard approach.

Three- Versus Five-Fraction Regimens of Stereotactic Body Radiotherapy for Peripheral Early-Stage Non-Small-Cell Lung Cancer: A Two-Institution Propensity Score-Matched Analysis.

PURPOSE: To evaluate differences in outcomes of early-stage peripheral non-small-cell lung cancer (NSCLC) treated with either 3- or 5-fraction stereotactic body radiotherapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Patients diagnosed with peripherally located early-stage NSCLC who received either a median dose of 60 Gy (interquartile range [IQR], 60-60, biologically effective dose, 151-151) in 3 fractions or a median dose of 50 Gy (IQR, 50-50, biologically effective dose, 94-94) in 5 fractions were included in this study. All data were retrospectively collected and reviewed in an institutional review board-approved database. RESULTS: A total of 192 lesions in 192 patients were identified: 94 received 3-fraction SBRT and 98 received 5-fraction SBRT. Patients in the 5-fraction cohort had significantly smaller tumors (P = .0021). Larger tumor size was associated with worse overall survival (hazard ratio, 1.40, P = .0013) for all patients. A single grade 3 toxicity was reported in each cohort. A propensity score-matched cohort of 94 patients was constructed with a median follow-up of 29.3 months (IQR, 17.3-44.6) for the 3-fraction cohort and 31.0 months (IQR, 17.0-48.5) for the 5-fraction cohort (P = .84). There were no statistically significant differences between these 2 cohorts in overall survival (P = .33), progression-free survival (P = .40), local failure (P = .86), and nodal or distant failure (P = .57) at 2 years. CONCLUSION: The 3- and 5-fraction SBRT regimens for early-stage peripheral NSCLC had comparable clinical outcomes. Both regimens were well tolerated. A large tumor size was an adverse prognostic factor for worse survival.