Impact of the COVID-19 pandemic on new starts to oral oncology medications in the US.

INTRODUCTION: The COVID-19 pandemic has had a significant impact on healthcare delivery. Although others have documented the impact on new cancer diagnoses, trends in new starts for oncology drugs are less clear. We examined changes in new users of oral oncology medications in the US following COVID-19 stay-at-home orders in 2020 compared to prior years. METHODS: We examined prescription data for members enrolled with a national pharmacy benefits manager in the US from January 1-October 31 of 2018, 2019, and/or 2020. This is a retrospective, observational study comparing new users per 100,000 members per month for all oral oncology drugs, and separately for breast, lung, and prostate cancer, leukemia, and melanoma oral drugs. We performed a difference-in-differences analysis for change in new users from pre-period (prior to pandemic-induced disruption, January-March), to post-period (following pandemic-induced disruption, April-October), between 2020 and 2019, and 2020 and 2018. RESULTS: New oral oncology drug users per 100,000 members per month declined by an additional 11.3% in the 2020 post-period compared to 2019 (p = 0.048). New oral breast cancer drug starts declined by an additional 14.0% in the 2020 post-period compared to 2019 (p = 0.040). Similar but non-significant trends were found between 2020 and 2018. No significant differences were found between post-period monthly new starts of leukemia, melanoma, lung or prostate cancer disease-specific oral medications. CONCLUSIONS: Long-term implications of delays in cancer treatment initiation are unclear, although there is concern that patient outcomes may be negatively impacted.

Tyrosine kinase inhibitor-associated syndrome of inappropriate secretion of anti-diuretic hormone.

Hyponatremia is a common complication among cancer patients. Certain antineoplastic agents have been associated with syndrome of inappropriate secretion of anti-diuretic hormone-induced hyponatremia. The most common agents associated with secretion of anti-diuretic hormone are vinca alkaloids, platinum compounds, and alkylating agents. We report a case of secretion of anti-diuretic hormone associated with tyrosine kinase inhibitors.

Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans.

BACKGROUND: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). METHODS: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. RESULTS: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. CONCLUSION: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.

The Feasibility of Using Point of Care Ultrasound as a Visual Substitute for Physical Examination During Telehealth Visits: A Pilot Project.

Telehealth provides greater opportunity for specialty access but lacks components of the physical exam. Point-of-care ultrasound (POCUS) may assist telehealth as a visual substitute for the provision of palpation. We conducted a prospective observational pilot project to survey oncologists about (1) their expectations of POCUS, (2) their use of POCUS in oncology telehealth visits, and (3) post-project assessment of their experiences. The results of the pre-assessment survey showed an interest among the oncologists in the ability to evaluate structures remotely via POCUS. POCUS was utilized in 6.4% of visits, most commonly for lymph node assessment (60% of use). POCUS was not utilized most often due to not being applicable to the patient's visit. There were 14 instances of technical issues limiting views of the relevant anatomy reported. Oncologists rated the use of POCUS as very satisfied or satisfied in the vast number of recorded responses. This pilot study suggests POCUS can be integrated into oncology telehealth visits for specific applications such as lymph node assessment. The surveys indicated a potential interest and positive responses that provide for the foundation of expansion to subspecialty care access for patients with telehealth supported by POCUS.

Teleoncology in the Veterans Health Administration: Models of Care and the Veteran Experience.

The Veterans Health Administration (VHA) has pioneered teleoncology to address access challenges faced by Veterans requiring cancer care. This ASCO Educational Book highlights the development of teleoncology programs within the VHA: the local VA Pittsburgh Healthcare System (VAPHS) Virtual Cancer Care Center, the National TeleOncology Program (NTO), and the regional Clinical Resource Hub (CRH) Oncology Program. These initiatives provide oncology care using a hub-and-spoke model, which centralizes expertise at hub sites and reaches Veterans at distant spoke sites through synchronous and asynchronous care. The deployment of these teleoncology programs has resulted in significant benefits, such as decreased travel for Veterans, high levels of patient satisfaction, and improved access to specialized treatments. Despite these advancements, disparities in teleoncology utilization and access to clinical trials persist. This educational manuscript highlights the successes and challenges of tele-oncology within the VHA, underscoring the critical role of telehealth in overcoming access barriers.

Developing national cancer survivorship standards to inform quality of care in the United States using a consensus approach.

PURPOSE: To develop United States (US) standards for survivorship care that informs (1) essential health system policy and process components and (2) evaluation of the quality of survivorship care. METHODS: The National Cancer Institute and the Department of Veterans Affairs led a review to identify indicators of quality cancer survivorship care in the domains of health system policy, process, and evaluation/assessment. A series of three virtual consensus meetings with survivorship care and research experts and advocates was conducted to rate the importance of the indicators and refine the top indicators. The final set of standards was developed, including ten indicators in each domain. RESULTS: Prioritized items were survivor-focused, including processes to both assess and manage physical, psychological, and social issues, and evaluation of patient outcomes and experiences. Specific indicators focused on developing a business model for sustaining survivorship care and collecting relevant business metrics (e.g., healthcare utilization, downstream revenue) to show value of survivorship care to health systems. CONCLUSIONS: The National Standards for Cancer Survivorship Care can be used by health systems to guide development of new survivorship care programs or services or to assess alignment and enhance services in existing survivorship programs. Given the variety of settings providing care to survivors, it is necessary for health systems to adapt these standards based on factors including age-specific needs, cancer types, treatments received, and health system resources. IMPLICATIONS FOR CANCER SURVIVORS: With over 18 million cancer survivors in the United States, many of whom experience varied symptoms and unmet needs, it is essential for health systems to have a comprehensive strategy to provide ongoing care. The US National Standards for Survivorship Care should serve as a blueprint for what survivors and their families can anticipate after a cancer diagnosis to address their needs.

Veterans Health Administration National TeleOncology Service.

PURPOSE: As the largest integrated health care system in the United States, the Veterans Health Administration (VA) is a leader in telehealth-delivered care. All 10 million Veterans cared for within the VA are eligible for telehealth. The VA cares for approximately 46,000 Veteran patients with newly diagnosed cancer and an estimated 400,000 prevalent cases annually. With nearly 38% of VA health care system users residing in rural areas and only 44% of rural counties having an oncologist, many Veterans lack local access to specialized cancer services. METHODS: We describe the VA's National TeleOncology (NTO) Service. NTO was established to provide Veterans with the opportunity for specialized treatment regardless of geographical location. Designed as a hub-and-spoke model, VA oncologists from across the country can provide care to patients at spoke sites. Spoke sites are smaller and rural VA medical centers that are less able to independently provide the full range of services available at larger facilities. In addition to smaller rural spoke sites, NTO also provides subspecialized oncology care to Veterans located in larger VA medical facilities that do not have subspecialties available or that have limited capacity. RESULTS: As of fiscal year 2021, 23 clinics are served by or engaged in planning for delivery of NTO and there are 24 physicians providing care through the NTO virtual hub. Most NTO physicians continue to provide patient care in separate traditional in-person clinics. Approximately 4,300 unique Veterans have used NTO services. Approximately half (52%) of Veterans using NTO lived in rural areas. Most of these Veterans had more than one remote visit through NTO. CONCLUSION: NTO is a state-of-the-art model that has the potential to revolutionize the way cancer care is delivered, which should improve the experience of Veterans receiving cancer care.

Overall survival based on oncologist density in the United States: A retrospective cohort study.

Medically underserved areas (MUA) or health professional shortage areas (HPSA) designations are based on primary care health services availability. These designations are used in recruiting international medical graduates (IMGs) trained in primary care or subspecialty (e.g., oncology) to areas of need. Whether the MUA/HPSA designation correlates with Oncologist Density (OD) and supports IMG oncologists' recruitment to areas of need is unknown. We evaluated the concordance of OD with the designation of MUAs/HPSAs and evaluated the impact of OD and MUA/HPSA status on overall survival. We conducted a retrospective cohort study of patients diagnosed with hematological malignancies or metastatic solid tumors in 2011 from the Surveillance Epidemiology and End Results (SEER) database. SEER was linked to the American Medical Association Masterfile to calculate OD, defined as the number of oncologists per 100,000 population at the county level. We calculated the proportion of counties with MUA or HPSA designation for each OD category. Overall survival was estimated using the Kaplan-Meier method and compared between the OD category using a log-rank test. We identified 68,699 adult patients with hematologic malignancies or metastatic solid cancers in 609 counties. The proportion of MUA/HPSA designation was similar across counties categorized by OD (93.2%, 95.4%, 90.3%, and 91.7% in counties with <2.9, 2.9-6.5, 6.5-8.4 and >8.4 oncologists per 100K population, p = 0.7). Patients' median survival in counties with the lowest OD was significantly lower compared to counties with the highest OD (8 vs. 11 months, p<0.0001). The difference remained statistically significant in multivariate and subgroup analysis. MUA/HPSA status was not associated with survival (HR 1.03, 95%CI 0.97-1.09, p = 0.3). MUA/HPSA designation based on primary care services is not concordant with OD. Patients in counties with lower OD correlated with inferior survival. Federal programs designed to recruit physicians in high-need areas should consider the availability of health care services beyond primary care.

Telehealth for Cancer Care in Veterans: Opportunities and Challenges Revealed by COVID.

The Veterans Health Administration system is one of the largest integrated health care providers in the United States, delivering medical care to > 9 million veterans. Barriers to delivering efficient health care include geographical limitations as well as long wait times. Telehealth has been used as a solution by many different health care services. However, it has not been as widely used in cancer care. In 2018, the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System expanded the use of telehealth to provide antineoplastic therapies to rural patients by creating a clinical video telehealth clinic of the Virtual Cancer Care Network. This allows oncologists located at the tertiary center to virtually deliver care to remote sites. The recent COVID-19 pandemic forced oncologists across the VA system to adopt telehealth to provide continuity of care. On the basis of our review and personal experience, we have outlined opportunities for telehealth to play a role in every step of the cancer care journey from diagnosis to therapy to surveillance to clinical trials for medical, surgical, and radiation oncology. There are many advantages, such as decreased travel time and potential cost savings; however, there continues to be challenges with veterans having access to devices and the Internet as well as understanding how to use telehealth equipment. The lessons learned from this assessment of the VA telehealth system for cancer care can be adopted and integrated into other health systems. In the future, there needs to be evaluation of how telehealth can be further incorporated into oncology, satisfaction of veterans using telehealth services, overcoming telehealth barriers, and defining metrics of success.

The Effect of Radium-223 Therapy in Agent Orange-Related Prostate Carcinoma.

BACKGROUND: Radium-223 (Ra-223) radioisotope has been reported to increase median survival in bone metastatic prostate carcinoma. The addition of Ra-223 to abiraterone was associated with an increased risk of bone fractures. There has been no comprehensive data for using Ra-223 in veterans who were exposed to Agent Orange (AO+). METHODS: We present a retrospective study of veterans with bone metastatic castration-resistant prostate cancer (CRPC) who received standard doses of Ra-223 and other sequential therapies at US Department of Veterans Affairs Pittsburgh Healthcare System in Pennsylvania from January 2014 to January 2019. Veterans were divided into 2 groups: those who were exposed to Agent Orange (AO+) and those who had no exposure (AO-). Time to study was calculated from the initiation of Ra-223. Time to skeletal-related events (SRE), progression of prostate specific antigen (PSA), bone metastasis, and alkaline phosphatase (ALP) were calculated in months using unpaired t test with 2-tailed P values. Median survival was calculated by Kaplan Meier R log-rank test. RESULTS: There were 34 veterans with bone metastatic CRPC: 17 veterans (50%) were AO+ and 17 veterans (50%) were AO-. The mean age of diagnosis of AO+ veterans was 62 years and 69 years (P = .005) for AO- veterans (the mean Gleason score 8.2 and 8.0, respectively [P = .71]). The median number of Ra-223 cycles was 6 (60%). Ten veterans received Ra-223 as first line (29%) and 24 veterans received Ra-223 later (71%). There were 12 SREs with median survival of 15 months. There was no difference in mean time to SRE between AO+ (8 veterans, 10.6 months) and AO- (4 veterans, 10.3 months) (P = .93). The mean time to PSA progression for AO+ was 5.4 months and AO- was 6.8 months (P = .28). Mean time to bone progression for AO+ was 7.6 months and AO- was 10.1 months (P = .16). Mean time to ALP progression for AO+ and AO- was 6.3 months and 8.7 months, respectively (P = .05). Twenty veterans (58%) had died. Median survival for Ra-223 first was 32 months and for Ra-223 later was 15 months (P = .14; hazard ratio [HR] 0.48; 95% CI, 0.17-1.3). Median survival for AO+ and AO- veterans was 12 months and 18 months, respectively (P = .15; HR, 2.0; 95% CI, 0.77-5.0). CONCLUSIONS: There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA, bone and ALP progression, even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between Ra-223 first vs Ra-223 later as well as between AO+ and AO- but there is a trend of worse survival in AO+ veterans.

A Rare Case of Sunitinib-Induced Rhabdomyolysis in Renal Cell Carcinoma.

We report a rare case of metastatic renal cell carcinoma (RCC) in a patient who developed rhabdomyolysis while on sunitinib. He was admitted to the hospital due to muscle weakness, fatigue, poor oral intake, and difficulty swallowing in March 2017. He was found to have pancytopenia, liver failure, kidney failure, high uric acid, and increased creatine phosphokinase of more than 5000. He quickly developed lactic acidosis and acute respiratory failure. He was transferred to the ICU, but his condition declined rapidly. He died 3 days later. In this article we discussed about sunitinib-mediated inhibition of adenosine monophosphate kinase (AMPK) as a possible pathophysiology of rhabdomyolysis. Our case is the third sunitinib-induced rhabdomyolysis reported in the literature.

VHA Practice Guideline Recommendations for Diffuse Gliomas.

Although histology still plays a critical role in diagnosing diffuse gliomas, additional ancillary testing is an essential tool for VA pathology laboratories.

Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System.

BACKGROUND: Dysfunctional mitochondrial processes limit malignant cells ability to use energy from fatty acids and ketones. Animal studies using ketogenic diets for cancer show encouraging results. We tested the diet's safety and feasibility in cancer patients across a broad variety of solid tumors. METHODS: We recruited 17 advanced cancer patients who were not on chemotherapy. They consumed 20 to 40 g of carbohydrates daily with evaluations performed weekly until week 4, then every 4 weeks until 16 weeks. Quality of life questionnaires monitored for tolerability and compliance. Positron emission/computerized tomography was ordered at baseline, 4,8 and 16 weeks. Student t-testing evaluated differences between baseline and last visit scores for quality of life, weight, body mass index, and serum parameters. Correlations between weight loss and serum ketones, glucose, lipids and creatinine were done. Two-tailed unpaired t-testing of the mean weight loss compared responders against non-responders. RESULTS: Eleven out of seventeen enrolled patients were evaluable. Mean age was 65+/- 11.7 years, weight 203 +/- 4.98 lbs. (92 ± 2.3 kgs.) and previous treatment failures was 1.7, +/- 0.97. All lost significant weight with hematologic, biochemical and lipid tests remaining stable. Quality of life scores slightly improved. At 4,8 and 16 weeks, six (54.5 %), five (45.4 %) and four (36 %) patients were stable or improved. We observed no correlations between serum glucose, ketones or lipids. Clinical response did not correlate with ketosis or glycemia. Responders (stable disease or partial responders) lost statistically more weight than non-responders. Dietary compliance was difficult. Only three patients continued dieting past 16 weeks. Out of these, two patients developed brain metastases and were on steroids. They survived 80 and 116 weeks respectively. The third patient underwent residual tumor resection and has no disease at 131 weeks. CONCLUSIONS: Modified Atkins diets are safe and feasible in advanced cancer. Quality of life was preserved. Patients who lost at least 10 % of their body weight responded the best. Steroid intake affected optimal ketone and glucose levels. Despite this, survival improved in some melanoma and lung cancer patients. Further studies are recommended. TRIAL REGISTRATION: Clinicaltrials.gov NCT01716468. Registered on September 18, 2012.

Erratum to: Modified Atkins diet in advanced malignancies-final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System.

[This corrects the article DOI: 10.1186/s12986-016-0113-y.].

Dispensing and Monitoring Oral Anticancer Therapy.

A VA Pittsburgh Healthcare System program to improve control of oral anticancer therapy medications has increased patient adherence, decreased toxicity, and reduced waste.

Cost-Effectiveness Analysis of Adjuvant Stage III Colon Cancer Treatment at Veterans Affairs Medical Centers.

The objective of this study was to evaluate the real-world cost effectiveness of adjuvant stage III colon cancer chemotherapy regimens, given that previous analyses have been based on data from clinical trials. The study was designed using integrated decision tree and Markov model, which was developed to evaluate the cost effectiveness of 5-fluorouracil/leucovorin (5-FU/LV), capecitabine, and the combination of each with oxaliplatin. The analysis was performed from a US Veterans Affairs perspective via retrospectively collected data, over a 5-year model time horizon. Outcome and cost data were used to calculate cost per quality adjusted life year (QALY), and one-way and probabilistic sensitivity analyses were performed. In the base case analysis, capecitabine and capecitabine plus oxaliplatin both cost more and were less effective than other regimens, and 5-FU/LV plus oxaliplatin, compared to 5-FU/LV alone, resulted in a cost of $25,997 per QALY gained. Model results were generally robust to parameter variation. Capecitabine plus oxaliplatin could be economically reasonable if full dosing occurred ≥76% of the time (base case 42%). In a real-world setting, the addition of oxaliplatin to 5-FU/LV is more effective but also more costly than 5-FU/LV alone. If full dosing of capecitabine-containing regimens can be assured, they may also be cost-effective strategies.

Lung cancer with gastrointestinal metastasis - review of theories of metastasis with three rare case descriptions.

Approximately 1 in 14 men and women during their lifetime will be diagnosed with lung cancer, which is the leading cause of cancer-related mortality in the world. As of January 1, 2008, there were about 373,500 men and women living with lung cancer in the United States. Fewer than 60,000 of these are estimated to be alive by January 2013, reflecting a poor overall 5-year relative survival rate of under 16 %. With metastatic cancer, the overall 5-year survival is meager 4 %. On the other hand, the overall five-year survival is over 50 % when the cancer is still in the localized stage. However, unfortunately, more than half of cases of lung cancer are diagnosed at an advanced stage Howlader et al. (2010). Cancer metastasis, the single most critical prognostic factor, is still poorly understood and a highly complex phenomenon. The most common sites of lung cancer metastasis are the lymph nodes, liver, adrenals, brain and bones. The gastrointestinal (GI) tract is an exceptionally rare site of metastasis; with only a handful of cases reported in the literature Centeno et al. (Lung Cancer, 18: 101-105, 1997); Hirasaki et al. (World J Gastroenterol, 14: 5481-5483, 2008); Carr and Boulos (Br J Surg, 83: 647, 1996); Otera et al. (Eur Respir Rev, 19: 248-252, 2010); Antler et al. (Cancer, 49: 170-172, 1982); Fujiwara et al. (Gen Thorac Cardiovasc Surg, 59: 748-752, 2011); Stinchcombe et al. (J Clin Oncol, 24: 4939-4940, 2006); John et al. (J Postgrad Med, 48: 199-200, 2002); Carroll and Rajesh (Eur J Cardiothorac Surg, 19: 719-720, 2001); Brown et al. (Dis Colon Rectum, 23: 343-345, 1980). We report three cases of non-small cell (squamous cell) lung cancer with GI tract metastasis-two in the colon and one in the jejunum. Then we present a review of literature exploring various theories of metastasis, as an attempt to understand the reason of preferential tumor metastasis.