Amro M. Abdelrahman, Ajit H. Goenka, Roberto Alva-Ruiz, Jennifer A. Yonkus, Jennifer L. Leiting, Rondell P. Graham, Kenneth W. Merrell, Cornelius A. Thiels, Christopher L. Hallemeier, Susanne G. Warner, Michael G. Haddock, Travis E. Grotz, Nguyen H. Tran, Rory L. Smoot, Wen Wee Ma, Sean P. Cleary, Robert R. McWilliams, David M. Nagorney, Thorvardur R. Halfdanarson, Michael L. Kendrick, and Mark J. Truty
Background: Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. Methods: We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). Results: We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P<.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13–0.40), and was highly correlated (P=.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor (P<.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9–153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2–0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1–0.4). Conclusions: Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.
Alex J. Ball, Imran Aziz, Sophie Parker, Ravishankar B. Sargur, Jonathan Aldis, and Matthew Kurien
Background: The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. Patients and Methods: Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 μg hemoglobin per gram of feces (μg/g). Results: A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 μg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 μg/g, respectively. The sensitivity of FIT at ≥10 μg/g to detect CRC was 91.1% (95% CI, 77.9%–97.1%); its specificity was 80.7% (95% CI, 79.3%–82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%–7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%–99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91–0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. Conclusions: Utilization of FIT at a threshold ≥10 μg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.
Michael J. Herriges Jr, Rachel Shenhav-Goldberg, Juliet I. Peck, Sumeet K. Bhanvadia, Alicia Morgans, Fumiko Chino, Thenappan Chandrasekar, Oleg Shapiro, Joseph M. Jacob, Alina Basnet, Gennady Bratslavsky, and Hanan Goldberg
Background: The term “financial toxicity” or “hardship” is a patient-reported outcome that results from the material costs of cancer care, the psychological impacts of these costs, and the coping strategies that patients use to deal with the strain that includes delaying or forgoing care. However, little is known about the impact of financial toxicity on cancer screening. We examined the effects of financial toxicity on the use of screening tests for prostate and colon cancer. We hypothesized that greater financial hardship would show an association with decreased prevalence of cancer screening. Methods: This cross-sectional survey–based US study included men and women aged ≥50 years from the National Health Interview Survey database from January through December 2018. A financial hardship score (FHS) between 0 and 10 was formulated by summarizing the responses from 10 financial toxicity dichotomic questions (yes or no), with a higher score associated with greater financial hardship. Primary outcomes were self-reported occurrence of prostate-specific antigen (PSA) blood testing and colonoscopy for prostate and colon cancer screening, respectively. Results: Overall, 13,439 individual responses were collected. A total of 9,277 (69.03%) people had undergone colonoscopies, and 3,455 (70.94%) men had a PSA test. White, married, working men were more likely to undergo PSA testing and colonoscopy. Individuals who had not had a PSA test or colonoscopy had higher mean FHSs than those who underwent these tests (0.70 and 0.79 vs 0.47 and 0.61, respectively; P≤.001 for both). Multivariable logistic regression models demonstrated that a higher FHS was associated with a decreased odds ratio for having a PSA test (0.916; 95% CI, 0.867–0.967; P=.002) and colonoscopy (0.969; 95% CI, 0.941–0.998; P=.039). Conclusions: Greater financial hardship is suggested to be associated with a decreased probability of having prostate and colon cancer screening. Healthcare professionals should be aware that financial toxicity can impact not only cancer treatment but also cancer screening.
Ishwarya Balasubramanian, Eric Finkelstein, Rahul Malhotra, Semra Ozdemir, Chetna Malhotra, and for the COMPASS Study Team
Background: Most studies describe the “average healthcare cost trend” among patients with cancer. We aimed to delineate heterogeneous trajectories of healthcare cost during the last 2 years of life of patients with a metastatic cancer and to assess the associated sociodemographic and clinical characteristics and healthcare use. Patients and Methods: We analyzed a sample of 353 deceased patients from a cohort of 600 with a solid metastatic cancer in Singapore, and we used group-based trajectory modeling to identify trajectories of total healthcare cost during the last 2 years of life. Results: The average cost trend showed that mean monthly healthcare cost increased from SGD $3,997 during the last 2 years of life to SGD $7,516 during the last month of life (USD $1 = SGD $1.35). Group-based trajectory modeling identified 4 distinct trajectories: (1) low and steadily decreasing cost (13%); (2) steeply increasing cost in the last year of life (14%); (3) high and steadily increasing cost (57%); and (4) steeply increasing cost before the last year of life (16%). Compared with the low and steadily decreasing cost trajectory, patients with private health insurance (β [SE], 0.75 [0.37]; P=.04) and a greater preference for life extension (β [SE], −0.14 [0.07]; P=.06) were more likely to follow the high and steadily increasing cost trajectory. Patients in the low and steadily decreasing cost trajectory were most likely to have used palliative care (62%) and to die in a hospice (27%), whereas those in the steeply increasing cost before the last year of life trajectory were least likely to have used palliative care (14%) and most likely to die in a hospital (75%). Conclusions: The study quantifies healthcare cost and shows the variability in healthcare cost trajectories during the last 2 years of life. Policymakers, clinicians, patients, and families can use this information to better anticipate, budget, and manage healthcare costs.
Joan How and Gabriela Hobbs
Interferons are cytokines with immunomodulatory properties that have been used in the treatment of myeloproliferative neoplasms (MPNs) for decades. However, their widespread use has been hampered by their adverse effect profile and difficulty with administration. Recently there has been a resurgence of interest in the use of interferons in MPNs given the development of pegylated formulations with improved tolerability. Currently, treatments for polycythemia vera (PV) and essential thrombocythemia (ET) are targeted toward decreasing the risk of thrombotic complications, because there are no approved therapies that are known to modify disease. However, recent data on interferons in MPNs have suggested the potential for disease-modifying activity, including the achievement of molecular remission and sustained clinical response. This development has led to the question of whether interferons should move forward as the preferred frontline cytoreductive agent for ET and PV, and challenges the criteria currently used to initiate therapy. We review randomized controlled trial data evaluating interferon’s efficacy and tolerability in patients with ET and PV. We then consider the data in the context of interferon’s known advantages and disadvantages to address whether interferons should be the first choice for cytoreductive treatment in patients with ET and PV.
Rongbo Lin, Jinfeng Zhu, Yushuang Luo, Xia Lv, Mingqian Lu, Haihui Chen, Huichao Zou, Zhichun Zhang, Shaowei Lin, Milu Wu, Xiaofeng Li, Min Zhou, Shen Zhao, Liyu Su, Jiang Liu, and Cheng Huang
Background: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. Methods: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. Results: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (P<.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 (P=.024) among the 3 arms. No severe adverse event occurred in any arm. Conclusions: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.
Aaron T. Gerds, Jason Gotlib, Haris Ali, Prithviraj Bose, Andrew Dunbar, Amro Elshoury, Tracy I. George, Krishna Gundabolu, Elizabeth Hexner, Gabriela S. Hobbs, Tania Jain, Catriona Jamieson, Paul R. Kaesberg, Andrew T. Kuykendall, Yazan Madanat, Brandon McMahon, Sanjay R. Mohan, Kalyan V. Nadiminti, Stephen Oh, Animesh Pardanani, Nikolai Podoltsev, Lindsay Rein, Rachel Salit, Brady L. Stein, Moshe Talpaz, Pankit Vachhani, Martha Wadleigh, Sarah Wall, Dawn C. Ward, Mary Anne Bergman, and Cindy Hochstetler
The classic Philadelphia chromosome–negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia. Assessment of symptoms at baseline and monitoring of symptom status during the course of treatment is recommended for all patients. This article focuses on the recommendations as outlined in the NCCN Guidelines for the diagnosis of MPN and the risk stratification, management, and supportive care relevant to MF.
Featured Updates to the NCCN Guidelines
Deborah K. Armstrong, Ronald D. Alvarez, Floor J. Backes, Jamie N. Bakkum-Gamez, Lisa Barroilhet, Kian Behbakht, Andrew Berchuck, Lee-may Chen, Viola C. Chitiyo, Mihaela Cristea, Maria DeRosa, Eric L. Eisenhauer, David M. Gershenson, Heidi J. Gray, Rachel Grisham, Ardeshir Hakam, Angela Jain, Amer Karam, Gottfried E. Konecny, Charles A. Leath III, Gary Leiserowitz, Joyce Liu, Lainie Martin, Daniela Matei, Michael McHale, Karen McLean, David S. Miller, Sanja Percac-Lima, Steven W. Remmenga, John Schorge, Daphne Stewart, Premal H. Thaker, Roberto Vargas, Andrea Wahner Hendrickson, Theresa L. Werner, Emese Zsiros, Mary A. Dwyer, and Lisa Hang
Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.