Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a prospective clinical trial and comparative analysis.

BACKGROUND: Open cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with high morbidity, which limits the degree to which patients may benefit from this therapy. This study aimed to determine the feasibility of laparoscopic CRS/HIPEC. METHODS: This was a single institution prospective clinical trial and comparative study using historical controls. Patients with histologically confirmed peritoneal surface malignancy (PSM) of appendiceal, colorectal, ovarian, or primary peritoneal origin, peritoneal carcinomatosis index (PCI) [Formula: see text] 10 were eligible. RESULTS: Clinical trial: 18 patients (median age 57 years, 39% female) with appendiceal (15) or colorectal (3) primary PSM underwent laparoscopic CRS/HIPEC. Median and range outcomes were: operative time 219 min (134-378), EBL 10 mL (0-100), time to return to bowel function 3 days (1-7), duration IV narcotic use 3 days (1-8), length of stay 6 days (3-11). All patients had a complete cytoreduction (CC-score 0). Three (17%) experienced minor morbidity, with no major morbidity or mortality. Median DFS and OS were not reached with median follow-up of 48 months. Comparative analysis: Laparoscopic approach associated with reduced time to return of bowel function (3 versus 4 days, p = 0.001), length of stay (8 versus 5 days, p < 0.001), and morbidity (16% versus 42%, p = 0.008). Independent predictors of DFS included prior chemotherapy (HR 5.07, 95% CI 1.85, 13.89; p = 0.002), and CC-score > 0 (HR 3.31, 95% CI 1.19, 9.41; p = 0.025), but not surgical approach. CC-score > 0 was the only independent predictor of OS (HR 10.12, 95% CI 2.16, 47.30, p = 0.003). CONCLUSIONS AND RELEVANCE: Laparoscopic CRS/HIPEC should be considered for patients with PSM with low-volume disease, including those with adenocarcinoma histology. TRIAL REGISTRATION: Clinicaltrials.gov; NCT02463877.

The impact of patient travel time on disparities in treatment for early stage lung cancer in California.

BACKGROUND: Travel time to treatment facilities may impede the receipt of guideline-concordant treatment (GCT) among patients diagnosed with early-stage non-small cell lung cancer (ES-NSCLC). We investigated the relative contribution of travel time in the receipt of GCT among ES-NSCLC patients. METHODS: We included 22,821 ES-NSCLC patients diagnosed in California from 2006-2015. GCT was defined using the 2016 National Comprehensive Cancer Network guidelines, and delayed treatment was defined as treatment initiation >6 versus ≤6 weeks after diagnosis. Mean-centered driving and public transit times were calculated from patients' residential block group centroid to the treatment facilities. We used logistic regression to estimate risk ratios and 95% confidence intervals (CIs) for the associations between patients' travel time and receipt of GCT and timely treatment, overall and by race/ethnicity and neighborhood socioeconomic status (nSES). RESULTS: Overall, a 15-minute increase in travel time was associated with a decreased risk of undertreatment and delayed treatment. Compared to Whites, among Blacks, a 15-minute increase in driving time was associated with a 24% (95%CI = 8%-42%) increased risk of undertreatment, and among Filipinos, a 15-minute increase in public transit time was associated with a 27% (95%CI = 13%-42%) increased risk of delayed treatment. Compared to the highest nSES, among the lowest nSES, 15-minute increases in driving and public transit times were associated with 33% (95%CI = 16%-52%) and 27% (95%CI = 16%-39%) increases in the risk of undertreatment and delayed treatment, respectively. CONCLUSION: The benefit of GCT observed with increased travel times may be a 'Travel Time Paradox,' and may vary across racial/ethnic and socioeconomic groups.

Evaluation of the Use of Cancer Registry Data for Comparative Effectiveness Research.

Importance: Researchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective, nonrandomized design of these analyses raises questions about study validity. Objective: To examine the extent to which comparative effectiveness analyses using observational cancer registry data produce results concordant with those of randomized clinical trials. Design, Setting, and Participants: In this comparative effectiveness study, a total of 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types were identified. Data on participants within the National Cancer Database (NCDB) diagnosed between 2004 and 2014, matching the eligibility criteria of the randomized clinical trial, were obtained. The present study was conducted from August 1, 2017, to September 10, 2019. The trials included 85 118 patients, and the corresponding NCDB analyses included 1 344 536 patients. Three Cox proportional hazards regression models were used to determine hazard ratios (HRs) for overall survival, including univariable, multivariable, and propensity score-adjusted models. Multivariable and propensity score analyses controlled for potential confounders, including demographic, comorbidity, clinical, treatment, and tumor-related variables. Main Outcomes and Measures: The main outcome was concordance between the results of randomized clinical trials and observational cancer registry data. Hazard ratios with an NCDB analysis were considered concordant if the NDCB HR fell within the 95% CI of the randomized clinical trial HR. An NCDB analysis was considered concordant if both the NCDB and clinical trial P values for survival were nonsignificant (P ≥ .05) or if they were both significant (P < .05) with survival favoring the same treatment arm in the NCDB and in the randomized clinical trial. Results: Analyses using the NCDB-produced HRs for survival were concordant with those of 141 randomized clinical trials in 79 univariable analyses (56%), 98 multivariable analyses (70%), and 90 propensity score models (64%). The NCDB analyses produced P values concordant with randomized clinical trials in 58 univariable analyses (41%), 65 multivariable analyses (46%), and 63 propensity score models (45%). No clinical trial characteristics were associated with concordance between NCDB analyses and randomized clinical trials, including disease site, type of clinical intervention, or severity of cancer. Conclusions and Relevance: The findings of this study suggest that comparative effectiveness research using cancer registry data often produces survival outcomes discordant with those of randomized clinical trial data. These findings may help provide context for clinicians and policy makers interpreting observational comparative effectiveness research in oncology.

A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain.

Background: A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy. Materials and Methods: A published Markov model comparing conventional therapies for painful diabetic neuropathy was modified to include arms for augmenting first-line, second-line (if first-line failed), or third-line (if first- and second-line failed) therapies with smoked cannabis. Microsimulation of 1,000,000 patients compared the cost (2017 U.S. dollars) and effectiveness (quality-adjusted life years [QALYs]) of usual care with and without adjunctive cannabis using a composite of third-party and out-of-pocket costs. Model efficacy inputs for cannabis were adapted from clinical trial data. Adverse event rates were derived from a prospective study of cannabis for chronic noncancer pain and applied to probability inputs for conventional therapies. Cannabis cost was derived from retail market pricing. Parameter uncertainty was addressed with one-way and probabilistic sensitivity analysis. Results: Adding cannabis to first-line therapy was incrementally less effective and costlier than adding cannabis to second-line and third-line therapies. Third-line adjunctive cannabis was subject to extended dominance, that is, the second-line strategy was more effective with a more favorable incremental cost-effectiveness ratio of $48,594 per QALY gained, and therefore, third-line adjunctive cannabis was not as cost-effective. At a modest willingness-to-pay threshold of $100,000/QALY gained, second-line adjunctive cannabis was the strategy most likely to be cost-effective. Conclusion: As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.

Types and Distribution of Payments From Industry to Physicians in 2015.

IMPORTANCE: Given scrutiny over financial conflicts of interest in health care, it is important to understand the types and distribution of industry-related payments to physicians. OBJECTIVE: To determine the types and distribution of industry-related payments to physicians in 2015 and the association of physician specialty and sex with receipt of payments from industry. DESIGN, SETTING, AND PARTICIPANTS: Observational, retrospective, population-based study of licensed US physicians (per National Plan & Provider Enumeration System) linked to 2015 Open Payments reports of industry payments. A total of 933 295 allopathic and osteopathic physicians. Outcomes were compared across specialties (surgery, primary care, specialists, interventionalists) and between 620 166 male (66.4%) and 313 129 female (33.6%) physicians using regression models adjusting for geographic Medicare-spending region and sole proprietorship. EXPOSURES: Physician specialty and sex. MAIN OUTCOMES AND MEASURES: Reported physician payment from industry (including nature, number, and value), categorized as general payments (including consulting fees and food and beverage), ownership interests (including stock options, partnership shares), royalty or license payments, and research payments. Associations between physician characteristics and reported receipt of payment. RESULTS: In 2015, 449 864 of 933 295 physicians (133 842 [29.8%] women), representing approximately 48% of all US physicians were reported to have received $2.4 billion in industry payments, including approximately $1.8 billion for general payments, $544 million for ownership interests, and $75 million for research payments. Compared with 47.7% of primary care physicians (205 830 of 431 819), 61.0% of surgeons (110 604 of 181 372) were reported as receiving general payments (absolute difference, 13.3%; 95% CI, 13.1-13.6; odds ratio [OR], 1.72; P < .001). Surgeons had a mean per-physician reported payment value of $6879 (95% CI, $5895-$7862) vs $2227 (95% CI, $2141-$2314) among primary care physicians (absolute difference, $4651; 95% CI, $4014-$5288). After adjusting for geographic spending region and sole proprietorship, men within each specialty had a higher odds of receiving general payments than did women: surgery, 62.5% vs 56.5% (OR, 1.28; 95% CI, 1.26-1.31); primary care, 50.9% vs 43.0% (OR, 1.38; 95% CI, 1.36-1.39); specialists, 36.3% vs 33.4% (OR, 1.15; 95% CI, 1.13-1.17); and interventionalists, 58.1% vs 40.7% (OR, 2.03; 95% CI, 1.97-2.10; P < .001 for all tests). Similarly, men reportedly received more royalty or license payments than did women: surgery, 1.2% vs 0.03% (OR, 43.20; 95% CI, 25.02-74.57); primary care, 0.02% vs 0.002% (OR, 9.34; 95% CI, 4.11-21.23); specialists, 0.08% vs 0.01% (OR, 3.67; 95% CI, 1.71-7.89); and for interventionalists, 0.13% vs 0.04% (OR, 7.98; 95% CI, 2.87-22.19; P < .001 for all tests). CONCLUSIONS AND RELEVANCE: According to data from 2015 Open Payments reports, 48% of physicians were reported to have received a total of $2.4 billion in industry-related payments, primarily general payments, with a higher likelihood and higher value of payments to physicians in surgical vs primary care specialties and to male vs female physicians.

Impact of insurance status and race on receipt of treatment for acoustic neuroma: A national cancer database analysis.

Acoustic neuroma (AN) management involves surgery, radiation, or observation. Previous studies have demonstrated that patient race and insurance status impact in-hospital morbidity/mortality following surgery; however the nationwide impact of these demographics on the receipt of each treatment modality has not been examined. The National Cancer Data Base (NCDB) from 2004 to 2013 identified AN patients. Multivariate analysis adjusted for several variables within each treatment modality, including patient age, race, sex, income, primary payer for care, tumor size, and medical comorbidities. Patients who were African-American (OR=0.7; 95%CI=0.5-0.9; p=0.01), elderly (minimum age 65) (OR=0.4; 95%CI=0.4-0.6; p<0.0001), on Medicare (OR=0.6; 95% CI=0.4-0.7; p=0.0005), or treated at a community hospital (OR=0.4; 95%CI=0.2-0.7; p=0.007) were less likely to receive surgery. Patients on Medicaid (OR=1.2; 95%CI=0.8-1.8; p=0.04) or treated at an integrated network (OR=1.2; 95%CI=0.9-1.6; p=0.0004) were more likely to receive surgery. Patients who were elderly (OR=2.2; 95%CI=1.7-2.9; p<0.0001) or treated in a comprehensive cancer center (OR=1.5; 95%CI=1.3-1.9; p=0.02) were more likely and Medicaid patients (OR=0.8; 95%CI=0.5-1.2; p=0.04) were less likely to receive radiation. Patients who were elderly (OR=2.2; 95%CI=1.7-2.7; p<0.0001), African-American (OR=1.5; 95%CI=1.1-2.0; p=0.01), on Medicare (OR=1.8; 95%CI=1.4-2.3; p=0.0003), or treated in a community hospital (OR=3.0; 95%CI=1.6-5.6; p=0.0007) were more likely to receive observation. Patients on Medicaid (OR=0.8; 95%CI=0.5-1.2; p=0.04) or treated in an integrated network (OR=0.8; 95%CI=0.6-1.0; p=0.0001) were less likely to receive observation. African-American race, elderly age, and community hospital treatment triaged towards observation/away from surgery; age also triaged towards radiation. Conversely, integrated networks triaged towards surgery/away from observation; comprehensive cancer centers triaged towards radiation. Medicaid insurance triaged towards surgery/away from radiation/observation; this may be detrimental since lack of private insurance is a known risk factor for increased in-hospital postoperative morbidity.

Approach to patients with pancreatic cancer without detectable metastases.

The poors outcomes associated with pancreatic cancer clearly reflect the advanced stage of disease at diagnosis for most patients. Through this lens, it is easy to lose sight of the fact that roughly 50% of patients with pancreatic cancer have no clinically detectable metastases at presentation. Herein, we discuss how patients with localized pancreatic cancer are currently managed. The primary goal of care for patients with resectable and borderline-resectable tumors is cure, facilitated by achieving margin-negative resection of the primary disease and delivering effective adjuvant and/or neoadjuvant therapy. For patients with locally advanced disease, the focus is on limiting local progression and outgrowth of metastatic disease and maintaining quality of life. Although it was once a centerpiece of therapy for localized pancreatic cancer, the value and place of radiation therapy in the treatment algorithm is now under increased scrutiny. In contrast, given its value as demonstrated in multiple prospective trials, chemotherapy is an established part of the treatment paradigm for all patients. With the demonstration that cytotoxic combinations such as fluorouracil, leucovorin, irinotecan, and oxaliplatin as well as gemcitabine/nab-paclitaxel are active in the metastatic setting, these agents are now being studied in patients with localized disease. The neoadjuvant setting provides a particularly favorable setting for evaluating new systemic strategies. Given the array of new targets, including immunomodulatory approaches, there is reason for optimism that we can markedly improve survival for all patients with pancreatic cancer and enter an era in which surgery with curative intent actually fulfills this goal on a much more regular basis.

Intensity-modulated radiotherapy for pancreatic adenocarcinoma.

PURPOSE: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. METHODS AND MATERIALS: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. RESULTS: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). CONCLUSIONS: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.