Barriers and facilitators to integrated cancer care between primary and secondary care: a scoping review.

PURPOSE: This scoping review identifies and characterises reported barriers and facilitators to providing integrated cancer care reported in the international literature, and develops recommendations for clinical practice. METHODS: This scoping review included literature published between 2009 and 2022 and describes the delivery of integrated cancer care between primary and secondary care sectors. Searches were conducted of an online database Ovid Medline and grey literature. RESULTS: The review included thirty-two papers. Barriers and facilitators to integrated cancer care were identified in three core areas: (1) at an individual user level around patient-healthcare professional interactions, (2) at an organisational level, and (3) at a healthcare system level. The review findings identified a need for further training for primary care professionals on cancer care, clarity in the delineation of primary care and oncologist roles (i.e. who does what), effective communication and engagement between primary and secondary care, and the provision of protocols and guidelines for follow-up care in cancer. CONCLUSIONS: Information sharing and communication between primary and secondary care must improve to meet the increasing demand for support for people living with and beyond cancer. Delivering integrated pathways between primary and secondary care will yield improvements in patient outcomes and health economic costs.

Humoral Immunity After COVID-19 Vaccination in Chronic Lymphocytic Leukemia and Other Indolent Lymphomas: A Single-Center Observational Study.

BACKGROUND: Chronic lymphocytic leukemia (CLL) and other non-Hodgkin's lymphomas (NHLs) lead to broad immunosuppression, conferring a greater risk for morbidity and mortality from SARS-CoV-2. Our study analyzed antibody (Ab) seropositivity from SARS-CoV-2 vaccination in patients with these cancers. METHODS: In the final analysis, 240 patients were involved, and seropositivity was defined as a positive total or spike protein Ab. RESULTS: Seropositivity was 50% in CLL, 68% in WM, and 70% in the remaining NHLs. Moderna vaccination led to higher seropositivity compared to Pfizer vaccination across all cancers (64% vs. 49%; P = .022) and specifically CLL patients (59% vs. 43%; P = .029). This difference was not explainable by differences in treatment status or prior anti-CD20 monoclonal Ab therapy. In CLL patients, current or prior cancer therapy led to lower seropositivity compared to treatment-naïve patients (36% vs. 68%; P = .000019). CLL patients treated with Bruton's tyrosine kinase (BTK) inhibitors had better seropositivity after receiving the Moderna vaccination compared to Pfizer (50% vs. 23%; P = .015). Across all cancers, anti-CD20 agents within 1 year led to a lower Ab response compared to greater than one year (13% vs. 40%; P = .022), a difference which persisted after booster vaccination. CONCLUSION: Antibody response is lower in patients with indolent lymphomas compared to the general population. Lower Ab seropositivity was found in patients with a history of anti-leukemic agent therapy or those immunized with Pfizer vaccine. This data suggests that Moderna vaccination may confer a greater degree of immunity against SARS-CoV-2 in patients with indolent lymphomas.

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma.

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

Health-related quality of life in early-stage Hodgkin lymphoma: a longitudinal analysis of the ABVD arm in the randomized controlled trial HD.6.

Early-stage Hodgkin lymphoma has become one of the most curable hematologic malignancies. Depending upon the disease location, possible toxicities, and patient preference, chemotherapy alone with ABVD remains an accepted treatment modality for this disease. There remains a paucity of data regarding the longitudinal trajectory of health-related quality of life (HRQoL) in patients treated for HL. The impact of disease and treatment on HRQoL is increasingly important to understand as the number of long-term survivors increases. We report the longitudinal HRQoL using data prospectively collected from diagnosis up to 10 years post-treatment in the ABVD arm of the HD.6 randomized controlled trial for early-stage HL patients (N=169). We analyzed HRQoL using the EORTC QLQ-C30 collected at baseline, 3 months, 6 months, and 12 months after completion of chemotherapy and yearly up to year 10. Clinically and statistically significant improvements were noted for specific domains including emotional (3 months post-treatment), social (12 months post-treatment) and financial functioning (2 years post-treatment), and the specific symptom of fatigue (6 months post-treatment) during the follow-up period. To our knowledge, this is the first prospective, longitudinal analysis of HRQoL specifically among patients with early-stage HL treated with ABVD therapy alone. Although improvements were noted, sustained clinically and statistically significant improvements were noted only in select symptoms emphasizing the need to better understand and optimize HRQoL among this patient group.

Cachexia is a risk factor for negative clinical and functional outcomes in patients receiving chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma.

Cachexia is a muscle-wasting syndrome that is known to impact the clinical course of several cancer populations but has not been specifically investigated in patients receiving chimeric antigen receptor T (CAR-T) cell therapy. In this study, we investigated the relationship between cachexia markers and several cancer and functional outcomes in a pilot population of aggressive B-cell non-Hodgkin lymphoma patients receiving CAR-T. We found that the prognostic nutritional index was linked to progression-free survival, overall survival, and disability-free survival, while several additional weight and serum-based markers of cachexia were also associated with negative outcomes. These data prompt further investigation of cachexia markers in populations receiving CAR-T cell therapy.

NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

Prevalence and determinants of depression up to 5 years after colorectal cancer surgery: results from the ColoREctal Wellbeing (CREW) study.

AIM: Depression experienced by people with colorectal cancer (CRC) is an important clinical problem affecting quality of life. Recognition of depression at key points in the pathway enables timely referral to support. This study aimed to examine depression before and 5 years after surgery to examine its prevalence and identify determinants. METHOD: The ColoREctal Wellbeing (CREW) study is a prospective UK cohort study involving 872 adults with nonmetastatic CRC recruited before surgery with curative intent. Questionnaires completed before surgery and 3, 9, 15, 24, 36, 48 and 60 months after surgery captured socio-demographics and assessed depression (Centre for Epidemiologic Studies Depression Scale, CES-D) and other psychosocial factors. Clinical details were also gathered. We present the prevalence of clinically significant depression (CES-D ≥ 20) over time and its predictors assessed before and 2 years after surgery. RESULTS: Before surgery, 21.0% of the cohort reported CES-D ≥ 20 reducing to 14.7% 5 years after surgery. Presurgery risk factors predicting subsequent depression were clinically significant depression and anxiety, previous mental health service use, low self-efficacy, poor health, having neoadjuvant treatment and low social support. Postsurgery risk factors at 2 years predicting subsequent depression were clinically significant depression, negative affect, cognitive dysfunction, accommodation type and poor health. CONCLUSION: Depression is highly pervasive in people with CRC, exceeding prevalence in the general population across follow-up. Our findings emphasize the need to screen and treat depression across the pathway. Our novel data highlight key risk factors of later depression at important and opportune time points: before surgery and at the end of routine surveillance. Early recognition and timely referral to appropriate support is vital to improve long-term psychological outcomes.

Unmet supportive care needs of breast, colorectal and testicular cancer survivors in the first 8 months post primary treatment: A prospective longitudinal survey.

OBJECTIVES: To explore the supportive care needs of cancer survivors, the characteristics of patients with high levels of unmet need, changes in unmet need after treatment ends and differences in unmet needs of breast, colorectal and testicular survivors. METHODS: The method used was a prospective longitudinal mailed survey. Unmet needs, measured by 25-item modified Cancer Survivors Unmet Needs survey at baseline (immediately post-treatment) and 8 months later, were analysed descriptively. RESULTS: Of 434 breast, 186 colorectal and 75 testicular patients responding at baseline, 56.2%, 65.6% and 50.7%, respectively, had no unmet needs, the top decile having ≥10 (breast) or seven (colorectal and testicular) different needs and seven different unmet needs. The most frequently reported unmet need (all groups) was fear of cancer recurrence. Unmet needs fell significantly at 8 months for breast patients. Some patients reported new needs. Needs were lowest amongst colorectal survivors and differed between the three groups. Higher levels of unmet needs (breast and colorectal) were associated with having had chemotherapy. CONCLUSION: Most survivors reported few unmet needs, but a small proportion have persisting or emerging needs. Routine or regular monitoring of unmet needs is required so that healthcare professionals can deliver personalised care based on individual needs, preferences and circumstances.

Hodgkin Lymphoma, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

PD-1/PD-L1 expression and interaction by automated quantitative immunofluorescent analysis show adverse prognostic impact in patients with diffuse large B-cell lymphoma having T-cell infiltration: a study from the International DLBCL Consortium Program.

Programmed cell death protein 1/programmed cell death protein ligand1 (PD-1/PD-L1) interaction is an important immune checkpoint targeted by anti-PD-1/PD-L1 immunotherapies. However, the observed prognostic significance of PD-1/PD-L1 expression in diffuse large B-cell lymphoma treated with the standard of care has been inconsistent and even contradictory. To clarify the prognostic role of PD-1/PD-L1 expression and interaction in diffuse large B-cell lymphoma, in this study we used 3-marker fluorescent multiplex immunohistochemistry and Automated Quantitative Analysis Technology to assess the CD3+, PD-L1+, and PD-1+CD3+ expression in diagnostic samples and PD-1/PD-L1 interaction as indicated by presence of PD-1+CD3+ cells in the vicinity of PD-L1+ cells, analyzed their prognostic effects in 414 patients with de novo diffuse large B-cell lymphoma, and examined whether PD-1/PD-L1 interaction is required for the prognostic role of PD-1+/PD-L1+ expression. We found that low T-cell tissue cellularity, tissue PD-L1+ expression (irrespective of cell types), PD-1+CD3+ expression, and PD-1/PD-L1 interaction showed hierarchical adverse prognostic effects in the study cohort. PD-1/PD-L1 interaction showed higher sensitivity and specificity than PD-1+ and PD-L1+ expression in predicting inferior prognosis in patients with high CD3+ tissue cellularity ("hot"/inflammatory tumors). However, both PD-1+ and PD-L1+ expression showed adverse prognostic effects independent of PD-1/PD-L1 interaction, and PD-1/PD-L1 interaction showed favorable prognostic effect in PD-L1+ patients without high CD3+ tissue cellularity. Macrophage function and tumor-cell MYC expression may contribute to the PD-1-independent adverse prognostic effect of PD-L1+ expression. In summary, low T-cell tissue cellularity has unfavorable prognostic impact in diffuse large B-cell lymphoma, and tissue PD-L1+ expression and T-cell-derived PD-1+ expression have significant adverse impact only in patients with high T-cell infiltration. PD-1/PD-L1 interaction in tissue is essential but not always responsible for the inhibitory effect of PD-L1+/PD-1+ expression. These results suggest the benefit of PD-1/PD-L1 blockade therapies only in patients with sufficient T-cell infiltration, and the potential of immunofluorescent assays and Automated Quantitative Analysis in the clinical assessment of PD-1/PD-L1 expression and interaction.

Controversies in the Approach to Initial Therapy of Hodgkin Lymphoma.

PURPOSE OF REVIEW: Availability of highly effective novel agents has altered the approach to initial therapy in patients with classical Hodgkin lymphoma (cHL). We will review controversies in the following areas: (1) the role of radiation in early unfavorable disease and the optimal treatment strategies for (2) advanced-stage disease and (3) elderly patients. RECENT FINDINGS: Strategies incorporating brentuximab vedotin into frontline treatment of cHL yielded favorable results in non-randomized elderly studies and were compared to ABVD in advanced disease among adults. Meanwhile, four cycles of escalated BEACOPP yielded unprecedented favorable results for the treatment of advanced disease in the German Hodgkin Study Group 18 study. The addition of novel agents to conventional treatment strategies has the potential to improve outcomes in high-risk groups of patients while reducing toxicity. The role of radiation therapy remains in question but may see diminished use with the incorporation of more effective agents in the frontline setting.

Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma.

CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP. We found that CD37 loss (CD37-) in ∼60% of DLBCL patients showed significantly decreased survival after R-CHOP treatment, independent of the International Prognostic Index (IPI), germinal center B-cell-like (GCB)/activated B-cell-like (ABC) cell of origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37-, including TP53 mutation, NF-κBhigh, Mychigh, phosphorylated STAT3high, survivinhigh, p63-, and BCL6 translocation. CD37 positivity predicted superior survival, abolishing the prognostic impact of high IPI and above biomarkers in GCB-DLBCL but not in ABC-DLBCL. Combining risk scores for CD37- status and ABC cell of origin with the IPI, defined as molecularly adjusted IPI for R-CHOP (M-IPI-R), or IPI plus immunohistochemistry (IHC; IPI+IHC) for CD37, Myc, and Bcl-2, significantly improved risk prediction over IPI alone. Gene expression profiling suggested that decreased CD20 and increased PD-1 levels in CD37- DLBCL, ICOSLG upregulation in CD37+ GCB-DLBCL, and CD37 functions during R-CHOP treatment underlie the pivotal role of CD37 status in clinical outcomes. In conclusion, CD37 is a critical determinant of R-CHOP outcome in DLBCL especially in GCB-DLBCL, representing its importance for optimal rituximab action and sustained immune responses. The combined molecular and clinical prognostic indices, M-IPI-R and IPI+IHC, have remarkable predictive values in R-CHOP-treated DLBCL.

NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.

Comorbidities are associated with poorer quality of life and functioning and worse symptoms in the 5 years following colorectal cancer surgery: Results from the ColoREctal Well-being (CREW) cohort study.

OBJECTIVE: More people are living with the consequences of cancer and comorbidity. We describe frequencies of comorbidities in a colorectal cancer cohort and associations with health and well-being outcomes up to 5 years following surgery. METHODS: Prospective cohort study of 872 colorectal cancer patients recruited 2010 to 2012 from 29 UK centres, awaiting curative intent surgery. Questionnaires administered at baseline (pre-surgery), 3, 9, 15, 24 months, and annually up to 5 years. Comorbidities (and whether they limit activities) were self-reported by participants from 3 months. The EORTC QLQ-C30 and QLQ-CR29 assessed global health/quality of life (QoL), symptoms, and functioning. Longitudinal analyses investigated associations between comorbidities and health and well-being outcomes. RESULTS: At baseline, the mean age of participants was 68 years, with 60% male and 65% colon cancer. Thirty-two per cent had 1 and 40% had ≥2 comorbidities. The most common comorbidities were high blood pressure (43%), arthritis/rheumatism (32%), and anxiety/depression (18%). Of those with comorbidities, 37% reported at least 1 that limited their daily activities. Reporting any limiting comorbidities was associated with poorer global health/QoL, worse symptoms, and poorer functioning on all domains over 5-year follow-up. Controlling for the most common individual comorbidities, depression/anxiety had the greatest deleterious effect on outcomes. CONCLUSIONS: Clinical assessment should prioritise patient-reported comorbidities and whether these comorbidities limit daily activities, as important determinants of recovery of QoL, symptoms, and functioning following colorectal cancer. Targeted interventions and support services, including multiprofessional management and tailored assessment and follow-up, may aid recovery of health and well-being in these individuals.

Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression.

Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30(+) NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov as #NCT01421667.

Hodgkin Lymphoma Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects.

Social support following diagnosis and treatment for colorectal cancer and associations with health-related quality of life: Results from the UK ColoREctal Wellbeing (CREW) cohort study.

OBJECTIVE: Social support is acknowledged as important in cancer survivorship, but little is known about change in support after cancer diagnosis and factors associated with this, particularly in colorectal cancer. The CREW cohort study investigated social support up to 2 years following curative intent surgery for colorectal cancer. METHODS: A total of 871 adults recruited pre-treatment from 29 UK centres 2010 to 2012 consented to follow-up. Questionnaires at baseline, 3, 9, 15, and 24 months post-surgery included assessments of social support (Medical Outcomes Study-Social Support Survey, MOS-SSS) and health-related quality of life (HRQoL). Socio-demographic, clinical and treatment details were collected. Longitudinal analyses assessed social support over follow-up, associations with participant characteristics, and HRQoL. RESULTS: Around 20% were living alone and 30% without a partner. Perceived social support declined in around 29% of participants, with 8% of these reporting very low levels overall from baseline to 2 years (mean MOS-SSS overall score < 40 on a scale from 0 to 100). Older age, female gender, greater neighbourhood deprivation, presence of co-morbidities, and rectal cancer site were significantly associated with reductions in perceived support. Poorer HRQoL outcomes (generic health/QoL, reduced wellbeing, anxiety, and depression) were significantly associated with lower levels of social support. CONCLUSIONS: Levels of social support decline following colorectal cancer diagnosis and treatment in nearly a third of patients and are an important risk factor for recovery of HRQoL. Assessment of support early on and throughout follow-up would enable targeted interventions to improve recovery, particularly in the more vulnerable patient groups at risk of poorer social support.

Nutritional care of older patients: experiences of general practitioners and practice nurses.

Older people living in the community face unique nutritional issues that put them at risk of undernutrition, which is associated with increased morbidity and mortality. Primary healthcare staff such as general practitioners (GPs) and practice nurses (PNs) are well placed to identify nutritional problems early and intervene. The aim of this study was to understand the experiences and current practices in a sample of GPs and PNs with regards to nutritional care of elderly patients. An online survey of GPs and PNs working in regional Victoria was conducted. Among the 45 respondents, 89% reported encountering consultations with a nutritional component for older patients within the previous 3 months, and 94% of those took some action, most commonly referrals, dietary advice or prescribing supplements. Although the majority (63%) felt confident in providing appropriate nutritional recommendations for patients, 68% reported a desire for further professional development in the area. Given the frequency of nutritional issues presenting, further work is required to determine how well equipped primary healthcare staff are to provide nutritional advice to older patients.

Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704.

Double hit lymphoma (DHL) and double protein-expressing (MYC, BCL2) lymphomas (DPL) fare poorly with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone); consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/-R with or without ASCT enabled evaluation of intensive consolidation. Immunohistochemistry (IHC) identified 27 of 198 patients (13·6%) with MYC overexpression; 20 (74%) harboured concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median 127 months follow-up, there is a trend favouring outcomes after ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT.