Patient, Caregiver, and Clinician Perspectives on Core Components of Therapeutic Alliance for Adolescents and Young Adults With Advanced Cancer: A Qualitative Study.

Importance: The patient-clinician therapeutic alliance is an important aspect of high-quality cancer care. However, components of the therapeutic alliance in adolescents and young adults (AYAs, aged 12-39 years) with cancer have not been defined. Objective: To identify components of and barriers to the therapeutic alliance between AYAs, caregivers, and clinicians from the perspective of all key stakeholders. Design, Setting, and Participants: In this qualitative study, semistructured in-depth interviews with patients, caregivers, and clinicians were conducted from 2018 to 2021 with no additional follow-up, with content analysis of resulting transcripts. Participants were recruited from Dana-Farber Cancer Institute, Kaiser Permanente Northern California, Kaiser Permanente Southern California, and an online cancer support community (Cactus Cancer Society). Eligible participants were English- or Spanish-speaking. Eligible patients were aged 12 to 39 years with stage IV or recurrent cancer. Eligible caregivers cared for an AYA living with advanced cancer or one who had died within 5 years. Eligible clinicians routinely provided care for AYAs with cancer. Main Outcomes and Measures: Perspectives on therapeutic alliance. Results: Interviews were conducted with 80 participants: 23 were patients (48% were female; 78% were White), 28 were caregivers (82% were female; 50% were White), and 29 were clinicians (69% were female; 45% were White). The mean (SD) age of patients was 29 (7.3) years. Interviews identified 6 components of therapeutic alliance: (1) compassion; (2) sense of connection; (3) clinician presence; (4) information sharing; (5) shared goals; and (6) individualization of care. While some domains were represented in prior models of therapeutic alliance, a unique domain was identified related to the need for individualization of the approach to care for AYA patients and their caregivers. Interviews also identified potential barriers to building the therapeutic alliance specific to the AYA population, including managing discordant needs between patients and caregivers and communication challenges at the end of life. Conclusions and Relevance: This study identified core components and barriers to building therapeutic alliance in the AYA advanced cancer population from the perspective of all the key stakeholders in the relationship. A novel component highlighting the need for individualization was identified. This model enables a deeper understanding of how to build therapeutic alliance in the AYA advanced cancer population, which may guide clinician training and facilitate improved care for this vulnerable population.

Inflammatory myofibroblastic tumor: A multi-institutional study from the Pediatric Surgical Oncology Research Collaborative.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

Appendectomy Versus Observation for Appendicitis in Neutropenic Children With Cancer.

BACKGROUND: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration. METHODS: Sites from the Pediatric Surgery Oncology Research Collaborative performed a retrospective review of children with NA over a 6-year period. RESULTS: Sixty-six children, with a median age of 11 years (range 1-17), were identified with NA while undergoing cancer treatment. The most common cancer diagnoses were leukemia (62%) and brain tumor (12%). Upfront appendectomy was performed in 41% of patients; the remainder had initial nonoperative management. Rates of abscess or perforation at diagnosis were equivalent in the groups (30% vs 24%; P = .23). Of patients who had initial nonoperative management, 46% (17 of 37) underwent delayed appendectomy during the same hospitalization. Delayed appendectomy was due to failure of initial nonoperative management in 65% (n = 11) and count recovery in 35% (n = 6). Cancer therapy was delayed in 35% (n = 23). Initial nonoperative management was associated with a delay in cancer treatment (46% vs. 22%, P = .05) and longer LOS (29 vs 12 days; P = .01). Patients who had initial nonoperative management and delayed appendectomy had a higher rate of postoperative complications (P < .01). CONCLUSIONS: In pediatric patients with NA from oncologic treatment, upfront appendectomy resulted in lower complication rates, reduced LOS, and fewer alterations in chemotherapy regimens compared to initial nonoperative management.

ISSLS Prize Winner: Dynamic Loading-Induced Convective Transport Enhances Intervertebral Disc Nutrition.

STUDY DESIGN: Experimental animal study of convective transport in the intervertebral disc. OBJECTIVE: To quantify the effects of mechanical loading rate on net transport into the healthy and degenerative intervertebral disc in vivo. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration is linked with a reduction in transport to the avascular disc. Enhancing disc nutrition is, therefore, a potential strategy to slow or reverse the degenerative cascade. Convection induced by mechanical loading is a potential mechanism to augment diffusion of small molecules into the disc. METHODS: Skeletally mature New Zealand white rabbits with healthy discs and discs degenerated via needle puncture were subjected to low rate axial compression and distraction loading for 2.5, 5, 10, 15, or 20 minutes after a bolus administration of gadodiamide. Additional animals with healthy discs were subjected to high-rate loading for 10 minutes or no loading for 10 minutes. Transport into the disc for each loading regimen was quantified using post-contrast-enhanced magnetic resonance imaging. RESULTS: Low-rate loading resulted in the rapid uptake and clearance of gadodiamide in the disc. Low-rate loading increased net transport into the nucleus by a mean 16.8% and 12.6% in healthy and degenerative discs, respectively. The kinetics of small molecule uptake and clearance were accelerated in both healthy and degenerative discs with low-rate loading. In contrast, high-rate loading reduced transport into nucleus by a mean 16.8%. CONCLUSION: These results illustrate that trans-endplate diffusion can be enhanced by forced convection in both healthy and degenerative discs in vivo. Mechanical loading-induced convection could offer therapeutic benefit for degenerated discs by enhancing uptake of nutrients and clearance of by-products. LEVEL OF EVIDENCE: 4.

Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo.

BACKGROUND CONTEXT: The intervertebral disc primarily relies on trans-endplate diffusion for the uptake of nutrients and the clearance of byproducts. In degenerative discs, diffusion is often diminished by endplate sclerosis and reduced proteoglycan content. Mechanical loading-induced convection has the potential to augment diffusion and enhance net transport into the disc. The ability of convection to augment disc transport is controversial and has not been demonstrated in vivo. PURPOSE: To determine if loading-induced convection can enhance small molecule transport into the intervertebral disc in vivo. STUDY DESIGN: Net transport was quantified via postcontrast enhanced magnetic resonance imaging (MRI) into the discs of the New Zealand white rabbit lumbar spine subjected to in vivo cyclic low rate loading. METHODS: Animals were administered the MRI contrast agent gadodiamide intravenously and subjected to in vivo low rate loading (0.5 Hz, 200 N) via a custom external loading apparatus for either 2.5, 5, 10, 15, or 20 minutes. Animals were then euthanized and the lumbar spines imaged using postcontrast enhanced MRI. The T1 constants in the nucleus, annulus, and cartilage endplates were quantified as a measure of gadodiamide transport into the loaded discs compared with the adjacent unloaded discs. Microcomputed tomography was used to quantify subchondral bone density. RESULTS: Low rate loading caused the rapid uptake and clearance of gadodiamide in the nucleus compared with unloaded discs, which exhibited a slower rate of uptake. Relative to unloaded discs, low rate loading caused a maximum increase in transport into the nucleus of 16.8% after 5 minutes of loading. Low rate loading increased the concentration of gadodiamide in the cartilage endplates at each time point compared with unloaded levels. CONCLUSIONS: Results from this study indicate that forced convection accelerated small molecule uptake and clearance in the disc induced by low rate mechanical loading. Low rate loading may, therefore, be therapeutic to the disc as it may enhance the nutrient uptake and waste product clearance.

Drug-induced changes to the vertebral endplate vasculature affect transport into the intervertebral disc in vivo.

Intervertebral disc health is mediated in part by nutrient diffusion from the microvasculature in the adjacent subchondral bone. Evidence suggests that a reduction in nutrient diffusion contributes to disc degeneration, but the role of the microvasculature is unclear. The purpose of this study was to induce changes in the endplate microvasculature in vivo via pharmaceutical intervention and then correlate microvasculature characteristics to diffusion and disc health. New Zealand white rabbits were administered either nimodipine (to enhance microvessel density) or nicotine (to diminish microvessel density) daily for 8 weeks compared to controls. Trans-endplate diffusion and disc health were quantified using post-contrast enhanced magnetic resonance imaging (MRI). Histology was utilized to assess changes to the subchondral vasculature. Results indicate that nimodipine increased vessel area and vessel-endplate contact length, causing a significant increase in disc diffusion. Surprisingly, nicotine caused increases in vessel number and area but did not alter diffusion into the disc. The drug treatments did affect the microvasculature and diffusion, but the relationship between the two is complex and dependent on multiple factors which include vessel-endplate distance, and vessel-endplate contact length in addition to vessel density. Our data suggest that drugs can modulate these factors to augment or diminish small molecule transport.