Building Efficiency and Scaling With a Remote Genetic Counseling Program.

Purpose A third-party telemedicine (TM) genetic counseling program was initiated at a large community oncology practice spanning 35 clinical sites with 110 clinicians and 97 advanced practice providers throughout Tennessee and Georgia. Patients and Methods Appropriate patients were referred through the electronic health record (EHR) based on current National Comprehensive Cancer Network guidelines. A combination of TM and genetic counseling assistants enhanced convenience, broadened access, and decreased no-show rates. Physician education for mutation-positive screening recommendations was provided through deep integration of dedicated genetic counseling notes in the EHR. Results From 2019 to 2022, the program expanded from 1 to 20 clinics with referrals growing from 195 to 885. An average of 82% of patients completed genetic counseling consultations over TM with more than 70% completing genetic testing. The average was 4 to 6 days from referral to consultation. The no-show rate was maintained at less than 7%. In 2023, this model supported all 35 clinics across the state. Conclusion Our program illustrates how remote genetic counseling programs are an effective choice for scaling genetics care across a large community oncology practice. Deep integration of TM genetic counseling within the EHR helps identify patients who are high risk and improves test adoption, patient keep rate, and turnaround time, helping to achieve better patient outcomes.

Real-world use and clinical impact of an electronic patient-reported outcome tool in patients with solid tumors treated with immuno-oncology therapy.

BACKGROUND: Utilization of electronic patient-reported outcome (ePRO) tools to monitor symptoms in patients undergoing cancer treatment has shown clinical benefits. Tennessee Oncology (TO) implemented an ePRO platform in 2019, allowing patients to report their health status online. We conducted a real-world, multicenter, observational, non-interventional cohort study to evaluate utilization of this platform in adults with solid tumors who initiated immuno-oncology (IO) therapy as monotherapy or in combination at TO clinics. METHODS: Patients initiating IO therapy prior to platform implementation were included in a historical control (HC) cohort; those initiating treatment after implementation were included in the ePRO cohort, which was further divided into ePRO users (platform enrollment ≤ 45 days from IO initiation) and non-users. Data were extracted from electronic medical records; patients were followed for up to 6 months (no minimum follow up). Outcomes included patient characteristics, treatment patterns, duration of therapy (DoT), and overall survival (OS). RESULTS: Data were collected for 538 patients in the HC and 1014 in the ePRO cohort; 319 in the ePRO cohort were ePRO users (uptake rate 31%). Baseline age was higher, more patients had stage IV disease at diagnosis, and more received monotherapy (82 vs 52%, respectively) in the HC vs the ePRO cohort. Median follow-up was 181.0 days (range 0.0-182.6) in the HC and 175.0 (0.0-184.0) in the ePRO cohort. Median DoT of index IO regimen was 5.1 months (95% confidence interval [CI], 4.4-NE) in the HC cohort vs not estimable (NE) in the ePRO cohort. Multivariable regression adjusting for baseline differences confirmed lower risk of treatment discontinuation in the ePRO vs HC cohort: hazard ratio (HR) 0.83 (95% CI, 0.71-0.97); p < 0.05. The estimated 6-month OS rate was 65.5% in the HC vs 72.4% in the ePRO cohort (p < 0 .01). Within the ePRO cohort, DoT of index IO regimen and OS did not differ between users and non-users. In ePRO users, patient platform use was durable over 6 months. CONCLUSION: Improvements in DoT and OS were seen after ePRO platform implementation. Conclusions are limited by challenges in separating the impact of platform implementation from other changes affecting outcomes.

Health care resource utilization, quality metrics, and costs of bladder cancer within the Oncology Care Model.

OBJECTIVES: New and emerging therapies have significantly changed the bladder cancer (BC) treatment landscape and can potentially affect spending and patient care in CMS' Oncology Care Model (OCM), a service delivery and payment model for voluntarily participating practices. The objectives of this analysis were to estimate health care resource utilization (HCRU) and benchmark spending per OCM episode of BC, and to model spending drivers and quality metrics. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort study was conducted of OCM episodes triggered by receipt of anticancer therapy among Medicare beneficiaries from 2016 to 2018. Based on this, an average performance estimation was conducted to assess the impact of hypothetical changes in novel therapy use by OCM practices. RESULTS: BC accounted for approximately 3% (n = 60,099) of identified OCM episodes. Relative to low-risk episodes, high-risk episodes were associated with greater HCRU and worse OCM quality metrics. Mean spending per high-risk episode was $37,857 (low-risk episode: $9204), with $11,051 spent on systemic therapies and $7158 on inpatient services. In the estimation, high- and low-risk BC exceeded the spending target by 1.7% and 9.4%, respectively. This did not affect payments to practices and no retrospective payments were necessary. CONCLUSIONS: As 3% of OCM episodes were attributed to BC, with only one-third classified as high-risk, controlling expenditure on novel therapies for advanced BC is unlikely to affect overall practice performance. The average performance estimation further emphasized the minimal impact that novel therapy spending in high-risk BC has on OCM payments to practices.

Impact of early detection on cancer curability: A modified Delphi panel study.

Expert consensus on the potential benefits of early cancer detection does not exist for most cancer types. We convened 10 practicing oncologists using a RAND/UCLA modified Delphi panel to evaluate which of 20 solid tumors, representing >40 American Joint Committee on Cancer (AJCC)-identified cancer types and 80% of total cancer incidence, would receive potential clinical benefits from early detection. Pre-meeting, experts estimated how long cancers take to progress and rated the current curability and benefit (improvement in curability) of an annual hypothetical multi-cancer screening blood test. Post-meeting, experts rerated all questions. Cancers had varying estimates of the potential benefit of early cancer detection depending on estimates of their curability and progression by stage. Cancers rated as progressing quickly and being curable in earlier stages (stomach, esophagus, lung, urothelial tract, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck) were estimated to be most likely to benefit from a hypothetical screening blood test. Cancer types rated as progressing quickly but having comparatively lower cure rates in earlier stages (liver/intrahepatic bile duct, gallbladder, pancreas) were estimated to have medium likelihood of benefit from a hypothetical screening blood test. Cancer types rated as progressing more slowly and having higher curability regardless of stage (prostate, thyroid) were estimated to have limited likelihood of benefit from a hypothetical screening blood test. The panel concluded most solid tumors have a likelihood of benefit from early detection. Even among difficult-to-treat cancers (e.g., pancreas, liver/intrahepatic bile duct, gallbladder), early-stage detection was believed to be beneficial. Based on the panel consensus, broad coverage of cancers by screening blood tests would deliver the greatest potential benefits to patients.

Bridging New Technology Into Clinical Practice With Mobile Apps, Electronic Patient-Reported Outcomes, and Wearables.

With sophisticated mobile and wearable technologies available, there has been interest in leveraging these devices to help gather and analyze patient-generated health data (PGHD). This information could be used to better address health concerns, aid in treatment decision-making, and guide interventional strategies to improve outcomes. Among PGHD, electronic patient-reported outcomes, direct reports of patient experience usually collected via validated scales and questionnaires, are increasingly integrated into routine clinical practice to monitor patient status. Electronic patient-reported outcomes have been shown to improve outcomes, including symptom control, quality of life, and overall survival, in several clinical trials. Electronic patient-reported outcome collection is now being implemented across broader clinical practice settings but with limited evaluation of impact thus far. Wearable devices and mobile apps provide opportunities to collect additional PGHD, including continuous physiologic measures, and to generate algorithms with which to monitor patients with cancer and guide interventions. In this article, we discuss several topics related to PGHD and technology, including electronic patient-reported outcomes, mobile apps, and wearable devices and how their introduction into oncology care has the potential to improve the collection and use of PGHD in the future. We also highlight the challenges and future directions needed for mobile and wearable technologies to provide meaningful information that can be acted upon and thus can improve oncologic care.

Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer.

OBJECTIVE: This randomized phase II study assessed the efficacy and safety of obatoclax mesylate, a small-molecule Bcl-2 inhibitor, added to carboplatin/etoposide chemotherapy as initial treatment for extensive-stage small-cell lung cancer (ES-SCLC). MATERIALS AND METHODS: Chemotherapy-naïve subjects with ES-SCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 received carboplatin/etoposide with (CbEOb) or without (CbE) obatoclax for up to six cycles. Responders to CbEOb could receive maintenance obatoclax until disease progression. The primary endpoint was objective response rate (ORR). RESULTS: 155 subjects (median age 62, 58% male, 10% ECOG PS 2) were treated with CbEOb (n=77) or CbE (n=78); 65% and 59% of subjects, respectively, completed six cycles. ORR was 62% with CbEOb versus 53% with CbE (1-sided p=0.143). Clinical benefit (ORR+ stable disease) trended better with CbEOb (81% versus 68%; p=0.054). Median progression-free survival (PFS) and overall survival (OS) were 5.8 months (95% confidence interval [CI]: 5.3-6.5) and 10.5 months (8.9-13.8) with CbEOb and 5.2 months (95% CI: 4.1-5.7) and 9.8 months (7.2-11.2) with CbE. Median OS was 10.5 months (95% CI: 8.9-13.8) and 9.8 months (7.2-11.2) with a nonsignificant hazard ratio for OS, 0.823; 1-sided p=0.121. Grade 3/4 adverse events (AEs) were primarily hematologic and similar in frequency between treatment arms. Obatoclax-related somnolence and euphoria were grade 1/2, transient, and did not require treatment discontinuation. CONCLUSION: Obatoclax was well tolerated when added to carboplatin/etoposide in first-line treatment of ES-SCLC, but failed to significantly improve ORR, PFS, or OS.

Phase I dosage finding and pharmacokinetic study of intravenous topotecan and oral erlotinib in adults with refractory solid tumors.

PURPOSE: Topotecan is widely used for refractory solid tumors but multi-drug resistance may occur due to tumor expression of ATP-binding cassette (ABC) transporters. Since erlotinib, an inhibitor of the epidermal growth factor receptor, also inhibits several ABC transporters, we performed a phase I study to evaluate the safety, efficacy, and pharmacokinetics of intravenous topotecan given in combination with erlotinib. METHODS: Patients received 150 mg of oral erlotinib daily and a 30 min intravenous infusion of topotecan on days 1-5 of a 21-day cycle. Dosage escalation of topotecan occurred with a starting dosage of 0.75 mg/m(2). The pharmacokinetics of topotecan was evaluated on day 1 of cycle 1 without erlotinib and on day 1 of cycle 2 or 3 with erlotinib. RESULTS: Twenty-nine patients were enrolled. The maximum tolerated dosage was determined to be 1.0 mg/m(2). Dose-limiting toxicities included neutropenia and thrombocytopenia. The average duration of treatment was 97 days. Two partial responses were observed. Topotecan clearance and exposure were similar with and without erlotinib. CONCLUSIONS: The combination of topotecan and erlotinib is tolerable at clinically effective doses. Erlotinib does not affect the disposition of topotecan to a clinically significant extent.

Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.

BACKGROUND: In this phase II study, we explored efficacy and toxicity of combined endocrine and low-dose metronomic chemotherapy therapy consisting of fulvestrant and capecitabine in estrogen and/or progesterone receptor-positive, HER2-negative MBC. PATIENTS AND METHODS: Patients with ≤ 1 previous hormonal treatment in the metastatic setting received an injection fulvestrant loading dose 500 mg on day 1, 250 mg on days 15 and 29 followed by 250 mg every 28 days along with continuous oral capecitabine in divided doses. The total fixed daily dose of capecitabine was either 1500 mg or 2000 mg, depending on the patient's weight (< 80 kg vs. ≥ 80 kg). Primary end points were PFS and TTP. Toxicity was assessed by continuous evaluations of treatment-emergent adverse events (AEs) and changes from baseline in laboratory values. RESULTS: Forty-one women, with a mean age of 64.5 years, were enrolled. Patients completed a median of 11 monthly treatment cycles. Median PFS was 14.98 months (95% confidence interval [CI], 7.26-upper limit [UL] not estimated) and median TTP was 26.94 months (95% CI, 7.26-UL not estimated). Median overall survival was 28.65 months (95% CI, 23.95-UL not estimated). Treatment was well tolerated with < 10% Grade 3 palmar-plantar erythrodysesthesia. Overall, the most frequent AEs were palmar-plantar erythrodysesthesia, fatigue, and nausea. CONCLUSION: Fulvestrant with metronomic capecitabine demonstrates substantial activity in hormone receptor-positive MBC and is well tolerated. Combined chemoendocrine approaches should be further explored considering the low toxicity of the combination with meaningful TTP.

The relation of trouble sleeping, depressed mood, pain, and fatigue in patients with cancer.

STUDY OBJECTIVES: To evaluate the relation among several symptoms that occur commonly in cancer patients: trouble sleeping, fatigue/sleepiness, depressed mood, and pain in a large cohort of cancer patients undergoing treatment in a community oncology practice. METHODS: Demographic, clinical, and patient reported outcomes data from 11,445 cancer patients undergoing treatment in a large community oncology practice were analyzed using structural equation modeling. The data were split so that a model was constructed using half of the patients; this model was then cross-validated on the remaining patients. RESULTS: Fatigue was best represented as a latent variable, and significant direct effects were found for trouble sleeping, depressed mood, and pain. Also, there were significant indirect effects of these variables on fatigue. The effect of depressed mood on fatigue and pain was mediated by trouble sleeping, and the effect of trouble sleeping on fatigue was mediated by pain. CONCLUSIONS: These results predict that interventions aimed at treatment of trouble sleeping, depressed mood, and pain will improve fatigue in patients with cancer. Further, these data predict that treatment of trouble sleeping will improve pain management in this population.

Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer.

PURPOSE: We conducted a phase II study of combination of the anti-insulin-like growth factor 1 receptor antibody CP-751,871 with paclitaxel and carboplatin (PCI) in advanced treatment-naïve non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomly assigned (2:1) to paclitaxel 200 mg/m(2), carboplatin (area under the plasma concentration-time curve of 6), and CP-751,871 10 to 20 mg/kg (PCI(10), PCI(20)) or paclitaxel and carboplatin alone (PC) every 3 weeks for up to six cycles. PCI(10-20) patients could continue CP-751,871 (figitumumab) treatment after chemotherapy discontinuation. Patients treated with PC experiencing disease progression were eligible to receive CP-751,871 at investigator's discretion. An additional nonrandomized single-arm cohort of 30 patients with nonadenocarcinoma tumor histology receiving PCI(20) was enrolled on completion of the randomized study. RESULTS: A total of 156 patients were enrolled onto the randomized portion of the study. Safety and efficacy information are available for 151 patients (98 patients treated with PCI and 53 patients treated with PC). Forty-eight patients treated with PCI received PCI(10) and 50 patients received PCI(20) in two sequential stages. Twenty of 53 patients treated with PC received CP-751,871 after disease progression. PCI was well tolerated. Fifty-four percent of patients treated with PCI and 42% of patients treated with PC had objective responses. Sixteen of 23 patients assessable for efficacy in the nonrandomized single-arm extension cohort also responded to treatment. Of note, 14 of 18 randomly assigned and 11 of 14 nonrandomly assigned patients treated with PCI with squamous cell carcinoma histology had response to treatment, including nine objective responses in bulky disease. Responses were also observed in two patients with squamous histology receiving CP-751,871 on PC discontinuation. PCI(20)/PC hazard ratio for progression-free survival was 0.8 to 0.56, according to censorship. CONCLUSION: These data suggest that PCI(20) is safe and effective in patients with NSCLC.

A phase II trial of pemetrexed and gemcitabine as first line therapy for poor performance status and/or elderly patients with stage IIIB/IV non-small cell lung cancer.

Pemetrexed and gemcitabine are both active agents for the treatment of locally advanced or metastatic NSCLC. We tested a novel biweekly combination of pemetrexed and gemcitabine for tolerability and efficacy in 45 elderly and/or poor performance status patients (44% female, mean age of 72.4 years) with measurable stage IIIB/IV NSCLC. Patients received biweekly cycles of pemetrexed 500 mg/m(2) IV over 10 min followed by gemcitabine 1500 mg/m(2) IV with vitamin B12 1000 microg IM, and folic acid 1mg po daily beginning 7 days before and continuing throughout treatment (median of 4 cycles). Ten patients experienced grade 3/4 neutropenia, two had grade 3 febrile neutropenia, and two had grade 3 anemia. Patients with ECOG PS 2 appeared poorly suited for the regimen, with 61.5% completing < or = 2 cycles. The overall response rate was 17.8%, the clinical benefit rate (CR+PR+SD >24 weeks) was 26.7%, and the median progression free survival was 3.5 months. However, ECOG 0-1 patients had longer PFS and tended to have a better response rate than ECOG 2 patients.

A phase I and pharmacokinetic study of TAS-108 in postmenopausal female patients with locally advanced, locally recurrent inoperable, or progressive metastatic breast cancer.

PURPOSE: TAS-108 is a novel steroidal anti-estrogen compound that has a strong binding affinity to the estrogen receptor and, in preclinical studies, has antitumor activity against tamoxifen-resistant breast cancer cell lines. The objective of this study was to investigate the safety and the pharmacokinetics in patients with previously treated advanced breast cancer. EXPERIMENTAL DESIGN: TAS-108 was administered orally once daily starting at 40 mg/day, with dose escalations of 60, 80, 120, and 160 mg/day. A minimum of three patients were enrolled in each dose level, and, if no drug-related grade 3 or higher adverse events were seen in the first 14 days, the next cohort of patients was treated at the next level. Pharmacokinetic data were obtained on day 1, 2, 15, and 28 of the first course. RESULTS: A total of 16 patients were enrolled, and most had received six to seven prior therapies. Clinical toxicities included nausea, vomiting, hot flashes, headache, weakness and fatigue; all were grade 1-2. TAS-108 had no effect on endometrial thickness based on trans-vaginal ultrasound evaluation. The average duration of therapy was 17.4 weeks (range, 4-60 weeks). The mean terminal half-life ranged from 8.0 to 10.7 hour in the interval of 12 to 24 hours postdose. The mean C(max) ranged from 2.8 to 21.0 ng/mL and AUC(0-t) from 15.1 to 148.7 ng.h/mL, this showed a linear correlation with the dose. CONCLUSIONS: TAS-108 was well tolerated in the doses studied with no maximum tolerated dose. The drug has linear pharmacokinetics, and in this heavily treated patient population, there was evidence of biological antitumor activity. A multi-institutional phase II study is planned.

Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence.

BACKGROUND: The goal of the current study was to assess the effect of pregnancy on the subsequent risk of recurrence after treatment for breast carcinoma, adjusting for established prognostic factors. METHODS: Between 1974 and 1998, 383 patients age < or =35 years were treated for breast carcinoma with adjuvant chemotherapy at The University of Texas M. D. Anderson Cancer Center (Houston, TX). The median follow-up period was 13 years. Of these, 13 patients were excluded from analysis, as no history was available regarding pregnancy; 240 (65%) were >30 years old; 47 (13%) had at least 1 pregnancy after therapy; 32 had full-term pregnancies; 10 had spontaneous or elective abortions; 4 had miscarriages; and 1 had a premature delivery. Estrogen receptor (ER) status, lymph node involvement, and disease stage were evaluated as potential risk factors for recurrence. Information on ER status was unavailable for 123 (33%) patients. RESULTS: Patients who experienced a pregnancy tended to have earlier-stage disease (Stage I/II: 80% vs. 73%), fewer positive lymph nodes (<4: 87% vs. 52%), more ER negativity (68% vs. 58%), and younger age (<30 years: 57% vs. 32%) than patients who did not. The incidence of disease recurrence was 23% for women who experienced a pregnancy and 54% for women who did not. The hazard ratio (using the multivariate Cox proportional hazards model) for disease recurrence in patients with posttreatment pregnancy was 0.71 (P=0.4). CONCLUSIONS: In the current study population, pregnancy was not associated with an increased risk of disease recurrence or poorer survival in patients previously treated for breast carcinoma.

Molecular targets in therapy for human soft-tissue and bone sarcomas.

Sarcomas represent a heterogeneous group of tumors with different natural histories and therapeutic approaches. Recent discoveries have identified molecular alterations in the pathogenesis of these tumors that lead to distinct effects on sarcoma cell biology. These tumor cell characteristics include independence from growth factors, evasion of apoptosis, and maintenance of genomic integrity. Inhibition of these molecular alterations represents a therapeutic opportunity to reverse the biologic basis of tumor formation in soft-tissue sarcomas and bone tumors.