Reporting time toxicity in prospective cancer clinical trials: A scoping review.

PURPOSE: This review aimed to assess the measurement and reporting of time toxicity (i.e., time spent receiving care) within prospective oncologic studies. METHODS: On July 23, 2023, PubMed, Scopus, and Embase were queried for prospective or randomized controlled trials (RCT) from 1984 to 2023 that reported time toxicity as a primary or secondary outcome for oncologic treatments or interventions. Secondary analyses of RCTs were included if they reported time toxicity. The included studies were then evaluated for how they reported and defined time toxicity. RESULTS: The initial query identified 883 records, with 10 studies (3 RCTs, 2 prospective cohort studies, and 5 secondary analyses of RCTs) meeting the final inclusion criteria. Treatment interventions included surgery (n = 5), systemic therapies (n = 4), and specialized palliative care (n = 1). The metric "days alive and out of the hospital" was used by 80% (n = 4) of the surgical studies. Three of the surgical studies did not include time spent receiving ambulatory care within the calculation of time toxicity. "Time spent at home" was assessed by three studies (30%), each using different definitions. The five secondary analyses from RCTs used more comprehensive metrics that included time spent receiving both inpatient and ambulatory care. CONCLUSIONS: Time toxicity is infrequently reported within oncologic clinical trials, with no standardized definition, metric, or methodology. Further research is needed to identify best practices in the measurement and reporting of time toxicity to develop strategies that can be implemented to reduce its burden on patients seeking cancer care.

Patient Perceptions of Care Coordination during Neoadjuvant Therapy for Gastrointestinal Cancers: A Mixed Methods Analysis.

PURPOSE: Effective cancer care coordination (CCC) is an integral component of health care delivery and critical to achieving optimal oncologic outcomes. Neoadjuvant therapy (NT), the delivery of multimodality therapy prior to surgery, is inherently complex and multidisciplinary, but CCC during NT is poorly understood. The objective of this study was to characterize patient perceptions of CCC during NT using a mixed methods approach. METHODS: This study is a cross-sectional analysis of patients with gastrointestinal cancers receiving NT who participated in a prospective longitudinal cohort study evaluating their real-time experience using a customized smartphone application. Patients completed the Cancer Care Coordination Questionnaire for Patients (CCCQ-P), a 20-item validated measure of care coordination quality, six weeks after initiating NT. Items were scored on a 5-point Likert scale, and subsections on communication (13 questions) and navigation (7 questions) were calculated with higher scores signifying better CCC. Univariate linear regression was used to calculate the impact of fragmented care and other factors on perceived CCC. Semi-structured interviews were conducted among a convenience sample of patients (n = 5); transcribed interviews were then coded using an inductive approach. RESULTS: Among 82 participants, mean age was 61 years old, 68% were male, and mean number of comorbidities was 1.68. Overall (mean 76.6 out of 100), communication subsection (48.6 out of 65), and navigation subsection (28.0 out of 35) CCCQ-P scores suggested overall positive perceptions of care coordination. Qualitative analysis of patient interviews highlighted the need for coordination among physicians before communicating the plan to patients as well as the importance of providers communicating plans in verbal and written form. CONCLUSIONS: Successful completion of NT requires significant care coordination between patients and healthcare professionals. Yet, in this cross-sectional analysis of patients on a prospective cohort study, patient perceptions of CCC during NT were overall positive. Future research should focus on optimizing other aspects of care delivery in order to improve outcomes of NT.

Quality of Life and Real-time Patient Experience During Neoadjuvant Therapy: A Prospective Cohort Study.

OBJECTIVE: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT). BACKGROUND: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers. METHODS: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT. RESULTS: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers. CONCLUSIONS: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers.

Evaluating the caregiver experience during neoadjuvant therapy for pancreatic ductal adenocarcinoma.

INTRODUCTION: Neoadjuvant therapy (NT) is increasingly recommended for patients with localized pancreatic ductal adenocarcinoma (PDAC). Recent research has highlighted the significant treatment burden that patients experience during NT, but caregiver well-being during NT is poorly understood. METHODS: A cross-sectional mixed-methods analysis of primary caregivers of patients with localized PDAC receiving NT was undertaken. All patients completed the Caregiver Quality of Life Index-Cancer (CQOLC) survey, while semi-structured interviews were conducted among a convenience sample of participants. RESULTS: Among 28 caregivers, the mean age was 60.1 years, and most were patient spouses/significant others (71.4%). Patients had resectable (18%), borderline resectable (46%), or locally advanced (36%) PDAC with a mean treatment duration of 2.9 months at the time of their caregiver's enrollment. Most caregivers felt that they received adequate emotional/psychosocial support (80%) and understood the rationale for NT (93%). A majority (60%) reported that caregiving responsibilities impacted their daily lives and required a decrease in their work hours, leading to financial challenges (47%). While overall QOL was moderate (mean 83 ± 21.1, range 0-140), "emotional burden" (47.3 ± 20.9), and "positive adaption" (57.3 ± 13.9) were the lowest ranked CQOLC subsection scores. DISCUSSION: Caregivers of patients with PDAC undergoing NT experience significant emotional symptoms and impact on their daily lives. Assessing caregiver needs and providing resources during NT should be a priority.

Surgeon Perspectives on the Management of Aborted Cancer Surgery: Results of a Society of Surgical Oncology Member Survey.

BACKGROUND: While surgery is generally necessary for most solid-organ cancers, curative-intent resection is occasionally aborted due to unanticipated unresectability or occult metastases. Following aborted cancer surgery (ACS), patients have unique and complex care needs and yet little is known about the optimal approach to their management. OBJECTIVE: The aim of this study was to define the practice patterns and perspectives of an international cohort of cancer surgeons on the management of ACS. METHODS: A validated survey assessing surgeon perspectives on patient care needs and management following ACS was developed. The survey was distributed electronically to members of the Society of Surgical Oncology (SSO). RESULTS: Among 190 participating surgeons, mean age was 49 ± 11 years, 69% were male, 61% worked at an academic institution, and most had a clinical practice focused on liver/pancreas (30%), breast (23%), or melanoma/sarcoma cancers (20%). Participants estimated that ACS occurred in 7 ± 6% of their cancer operations, most often due to occult metastases (67%) or local unresectability (30%). Most surgeons felt (very) comfortable addressing their patients' surgical needs (92%) and cancer treatment-related questions (90%), but fewer expressed comfort addressing psychosocial needs (83%) or symptom-control needs (69%). While they perceived discussing next available therapies as the patients' most important priority after ACS, surgeons reported avoiding postoperative complications as their most important priority (p < 0.001). While 61% and 27% reported utilizing palliative care and psychosocial oncology, respectively, in these situations, 46% noted care coordination as a barrier to addressing patient care needs. CONCLUSIONS: Results from this SSO member survey suggest that ACS is relatively common and associated with unique patient care needs. Surgeons may feel less comfortable assessing psychosocial and symptom-control needs, highlighting the need for novel patient-centered approaches.

Impact of early vs late palliative care referrals on healthcare utilization in patients with pancreatic cancer.

PURPOSE: The purpose of this study was to examine the impact of early versus late palliative care referral (PCR) following pancreatic cancer diagnosis. METHODS: Patients diagnosed with PDAC who received a PCR between 2014 and 2020 at a major academic institution were identified. PCR was classified as early (< 30 days) or late (≥ 30 days) based on time from definitive diagnosis. Data were obtained on number of emergency department (ED) visits, intensive care unit (ICU) admissions, and hospital admissions. RESULTS: Among 1458 patients with PDAC, 419 (28.7%) received PCR, among which 67.3% (n = 282) received a late PCR. Of those who received PCR, the majority were White (85%) and male (54.8%), with a median age of 62 years at time of diagnosis. Patients who received an early PCR more commonly presented with stage 4 disease at diagnosis (early: n = 91, 69% vs. late: n = 132, 47%), whereas patients who received a late PCR more commonly presented with stage 1, 2, or 3 disease (early: n = 40, 30.5% vs. late: n = 150, 53.2%) (p < 0.001). Patients who received early PCR had fewer median ED visits (1 vs. 2, p < 0.001) and hospital admissions (1 vs. 2, p < 0.001) compared with patients who received late PCR. However, after performing recurrent-event Cox-proportional hazards models, the timing of PCR did not impact hospital admission (HR 0.88, 95% CI 0.68, 1.14; p = 0.3). CONCLUSION: Timing of PCR for patients with PDAC was not associated with healthcare utilization. Further prospective trials are needed to study the patient-centered impact of early integration of palliative care services into multidisciplinary pancreatic cancer teams.

Characterizing treatment burden during neoadjuvant therapy for patients with gastrointestinal cancer: A mixed methods analysis.

INTRODUCTION: Neoadjuvant therapy (NT) is increasingly used before surgery for patients with gastrointestinal (GI) cancers. Treatment burden is a patient-centered measure defined as the work of being a patient and characterizes the impact of medical treatment on one's functioning and well-being. While treatment burden has previously been studied in chronic diseases and cancer survivorship, the treatment burden of undergoing NT is unknown. METHODS: All patients enrolled in a prospective cohort study evaluating the real-time experience of NT for GI cancers completed either the Patient Experience with Treatment and Self-management (PETS) survey, a 46-item validated measure of treatment burden, or the mini-PETS questionnaire. PETS subsections were scored on a 5-point Likert scale and then standardized on a 100-point scale (a higher number means more treatment burden). Semistructured interviews were conducted among a convenience sample of patients (n = 5); qualitative data were coded and then analyzed using an integrated approach. RESULTS: Among 126 participants, the mean age was 59 years old, 61% were male, and the mean number of comorbidities was 1.57. The most common cancers were colorectal (46%) and pancreatic (28%). The mean length of NT treatment was 3.7 months and 80.2% of patients underwent surgical resection following NT. The highest standardized treatment burden scores were observed in healthcare services (44 ± 15), social limitations (44 ± 26), exhaustion (41 ± 23), and medical expenses (40 ± 18) whereas the lowest scores were reported in medication use (19 ± 16) and interpersonal challenges (19 ± 17). Commonly experienced emotional symptoms were feeling worn out (43%) or frustrated (32%). No significant differences were observed in mean treatment burden subscores between patients who underwent surgery versus those who did not. Qualitative analysis of treatment burden during NT identified common themes of impact on normal life activities, challenges with healthcare access, impact on relationships, and significant physical and emotional symptoms. CONCLUSIONS: NT is associated with a significant treatment burden, particularly in the domains of accessing healthcare services, social limitations, and exhaustion. Given the increasing use of NT for GI cancers, novel patient-centered approaches are needed to improve quality of life and ensure the completion of multimodality therapy.

Utilization of Palliative and Hospice Care Among Pancreatic Cancer Patients at an Academic Center.

INTRODUCTION: Pancreatic ductal adenocarcinoma has the lowest 5-y relative survival of all solid tumor malignancies. Palliative care can improve the quality of life of both patients and their caregivers. However, the utilization patterns of palliative care in patients with pancreatic cancer are unclear. METHODS: Pancreatic cancer patients who were diagnosed between October 2014 and December 2020 at the Ohio State University were identified. Palliative care and hospice utilization and referral patterns were assessed. RESULTS: Of the 1458 pancreatic cancer patients, 55% (n = 799) were male, median age at diagnosis was 65 y (interquartile range [IQR]: 58, 73), and most were Caucasian (n = 1302, 89%). Palliative care was utilized by 29% (n = 424) of the cohort, with the initial consultation obtained after an average of 6 ± 9 mo from diagnosis. Patients who received palliative care were younger (62 y, IQR: 55, 70 versus 67 y, IQR: 59, 73; P < 0.001) and more frequently members of racial and ethnic minorities (15% versus 9%; P < 0.001) versus those who did not receive palliative care. Among the 344 (24%) patients who received hospice care, 153 (44%) had no prior palliative care consultation. Patients referred to hospice care survived a median of 14 d (95% CI, 12-16) after hospice referral. CONCLUSIONS: Only 3 out of 10 patients with pancreatic cancer received palliative care at an average of 6 mo from initial diagnosis. More than two out of every five patients referred to hospice had no previous palliative care consultation. Efforts to understand the impact of improved integration of palliative care into pancreatic cancer programs are needed.

Medical Face Masks Do Not Affect Acid-Base Balance Yet Might Facilitate the Transmission of Staphylococcus aureus in Hospital Settings during the COVID-19 Pandemic.

INTRODUCTION: Due to the SARS-CoV-2 coronavirus pandemic, the wearing of masks has become a common phenomenon. Most of the undesirable effects of using a protective face covering are usually related to the prolonged time of its wearing, and the adverse consequences of face coverings should be considered two-fold. The aim of the study was to evaluate the rate of contamination of the three types of face coverings (surgical, N95, and FFP2 masks) with the microorganism-aerobic bacteria, yeasts, and molds-after the 3 h exposure time. The study aimed to investigate the effects of wearing FFP2 masks (KN95) on respiratory function and the acid-base balance of the human body. RESULTS: The presence of S. aureus was confirmed in both nasal carriers and non-carriers which may demonstrate the cross-contamination and spread of this bacterium via hands. S. aureus was found on external and internal surfaces of face masks of each type, and therefore could also be transmitted via hands from external sources. The 3 h exposure time is not sufficient for Gram-negative rods and mold contamination. Moreover, there were no significant differences in most of the parameters studied between the first and second examinations, both in spirometry and capillary blood gas analysis (p > 0.05).

Patient Preferences for Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Physicians are increasingly recommending neoadjuvant therapy (NT) before surgery for pancreatic ductal adenocarcinoma (PDAC). However, patient preferences for and opinions regarding NT are poorly understood. METHODS: Survivors and caregivers from a national PDAC patient advocacy organization completed an online survey assessing preferences for NT versus surgery first (SF) and factors influencing their decision making. RESULTS: Among 54 participants, 74.1% had a personal history of PDAC. While most patients preferred SF for resectable disease, NT was the preferred treatment approach for borderline resectable, locally advanced, and resectable cancers with high carbohydrate antigen 19-9. The most important factor influencing patient decision making regarding NT was its impact on overall survival while the least important was published national guidelines. The most preferred rationale for NT was ability to downstage to surgical resection and early treatment of micrometastatic disease. CONCLUSIONS: Among a national cohort of PDAC survivors and caregivers, the majority preferred SF for resectable PDAC, whereas NT was preferred when the resectability of a tumor was in question. The impact of NT on quantity and quality of life, as well as the likelihood of achieving surgical resection, was most highly valued by participants.

Patient Perspectives on Defining Textbook Outcomes Following Major Abdominal Surgery.

BACKGROUND: The composite metric textbook outcome (TO) has recently gained interest as a novel quality measure. However, the criteria for defining a TO have not been rigorously defined and patient perspectives on the characteristics of TO are unknown. METHODS: Patients who underwent major abdominal surgery at a single tertiary care center were administered a customized survey designed to ascertain their perspectives on defining TOs. The relationship between patient-reported and clinically defined TO rates was compared. RESULTS: Among 79 patients who underwent gastrointestinal (51%), pancreatic (29%), hepatic (18%), or other major abdominal (3%) operations, 57% were female and 86% had an ASA class ≥3. Most patients underwent surgery for malignancy (87%) with 60% undergoing an open operation. Patients most commonly valued no mortality following surgery (96%), no reoperation (75%), and having a margin negative resection (73%) as "extremely important." In contrast, those outcomes that were most commonly valued as "not important at all" or "minimally important" were receiving a blood transfusion (24%) and not having any complications (13%). Using previously published criteria for TOs, 47 (60%) patients were classified as having a clinically defined TO; in contrast, 68 patients (86%) self-reported their outcome was textbook. Self-reported responses were concordant with clinically defined TO criteria 63% of the time (McNemar's test: S=15.2, p<0.01, evidence of disagreement). CONCLUSION: There was significant discordance between patient-reported versus clinically defined measures of TOs, suggesting patients value other considerations beyond traditional factors when evaluating the success of their surgery. Future studies should delineate these relationships and incorporate these factors to refine TO definitions.

Prospective pilot study protocol evaluating the safety and feasibility of robot-assisted nipple-sparing mastectomy (RNSM).

INTRODUCTION: Nipple-sparing mastectomy (NSM) can be performed for the treatment of breast cancer and risk reduction, but total mammary glandular excision in NSM can be technically challenging. Minimally invasive robot-assisted NSM (RNSM) has the potential to improve the ergonomic challenges of open NSM. Recent studies in RNSM demonstrate the feasibility and safety of the procedure, but this technique is still novel in the USA. METHODS AND ANALYSIS: This is a single-arm prospective pilot study to determine the safety, efficacy and potential risks of RNSM. Up to 12 RNSM will be performed to assess the safety and feasibility of the procedure. Routine follow-up visits and study assessments will occur at 14 days, 30 days, 6 weeks, 6 months and 12 months. The primary outcome is to assess the feasibility of removing the breast gland en bloc using the RNSM technique. To assess safety, postoperative complication information will be collected. Secondary outcomes include defining benefits and challenges of RNSM for both surgeons and patients using surveys, as well as defining the breast and nipple-areolar complex sensation recovery following RNSM. Mainly, descriptive analysis will be used to report the findings. ETHICS AND DISSEMINATION: The RNSM protocol was reviewed and approved by the US Food and Drug Administration using the Investigational Device Exemption mechanism (reference number G200096). In addition, the protocol was registered with ClinicalTrials.gov (NCT04537312) and approved by The Ohio State University Institutional Review Board, reference number 2020C0094 (18 August 2020). The results of this study will be distributed through peer-reviewed journals and presented at surgical conferences. TRIAL REGISTRATION NUMBER: NCT04537312.

Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naïve pancreatic cancer patients.

BACKGROUND: Cancer-associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer-induced cachexia in patients with earlier stages of disease. METHODS: A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high-sensitivity multiplex was used for increased sensitivity for nine cytokines. RESULTS: Resectable pancreatic cancer patients with cachexia had low levels of canonical pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interferon-γ (IFN-γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein-1 (MCP-1) was increased in treatment-naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to be decreased in the same cohort of treatment-naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers. CONCLUSIONS: Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment-naïve patients have higher levels of MCP-1, suggesting that MCP-1 may be useful as a biomarker of cancer cachexia.