JCO Global Oncology最新文献

Purpose: Sub-Saharan Africa carries one of the highest burdens of hepatocellular carcinoma (HCC) in the world, with hepatitis B virus (HBV) as the most common cause. Studies in several regions of the world suggest important cancer differences in rural versus urban settings, but limited studies have been performed in Africa.

Methods: We performed a scoping review and pooled analysis of studies on HCC in Africa. Using land use data from the European Space Agency, we calculated the distance in kilometers from each study site to the nearest rural area. Regression models were fit to estimate the association between distance to the nearest rural area and HBV, sex, and weighted mean age.

Results: Data from 57 studies including 10,907 patients across 36 towns/cities were included in our analysis. Proximity to rural areas was associated with a higher frequency of HBV-associated HCC in assessment of distance both at midpoint and at quartiles after controlling for country: risk ratio (RR) 1.71 (95% CI, 1.52 to 1.93) and RR 1.51 (95% CI, 1.25 to 1.84), respectively. No association was found between sex and proximity to a rural area: RR 1.02 (95% CI, 0.96 to 1.08). The weighted mean age across the four distance quartiles was 50.09, 53.43, 47.98, and 53.35 years with no statistically significant difference found across the quartiles (P = .81).

Conclusion: Individuals living in rural Africa have a higher rate of HBV-related HCC compared with other liver diseases. Increased HBV awareness efforts in these areas should be considered.

Purpose: This study aimed to differentiate nonscheduled visits (NSVs) in an outpatient palliative care setting that are driven by or accompanied by uncontrolled symptoms from those that are administrative or routine, such as prescription refills and examination readings. A small language model (SLM) was used to enhance the detection and management of symptoms, thus improving health care resource allocation.

Methods: A retrospective analysis was performed on 25,867 patient visits to an outpatient palliative care unit, including 7,036 NSVs. A stratified random sample of 384 NSVs was reviewed to determine the presence of symptoms, using physician audits as the gold standard. A Phi-3-based SLM was validated against these audits to assess its accuracy in detecting the symptoms. The validated SLM was then applied to the entire NSV data set to identify symptom patterns. Multivariate linear regression was used to analyze the association of age, cancer type, and insurance category with the presence of symptoms.

Results: SLM demonstrated high sensitivity (99.4%) and accuracy (95.3%) in identifying symptom-driven NSVs. The analysis revealed that 85.7% of the NSVs were driven by symptoms, indicating a significant hidden burden of unmanaged symptoms. The study found that certain demographic and clinical factors, including younger age groups and specific cancer types, were significantly associated with an increased symptom burden.

Conclusion: This study highlights the substantial burden of symptom-driven NSVs in palliative care and demonstrates the effectiveness of using a SLM to identify and manage symptoms. Implementing such models in clinical practice can improve patient care by optimizing the allocation of health care resources and tailoring interventions to the needs of patients with advanced illnesses.

Purpose: Patients with diffuse large B-cell lymphoma (DLBCL) who are treated in low-resource settings have inferior outcomes compared with those in high-resource settings. Rituximab, an anti-CD20 monoclonal antibody, when combined with chemotherapy, improves overall survival (OS) for DLBCL. However, in part due to the limited availability of infusion centers in low-resource countries, rituximab is rarely used. Subcutaneous rituximab (sqR) is a potential solution; however, its safety and efficacy have not been tested in low-income countries.

Methods: This open-label phase I study enrolled patients 18 years or older with newly diagnosed DLBCL. The first cohort (n = 6) received intravenous rituximab plus CHOP. This cohort received sqR for subsequent cycles. The second cohort (n = 12) received sqR plus CHOP for all cycles. Safety and tolerability were evaluated; secondary outcomes included response rates and treatment completion.

Results: Between October 25, 2019, and October 7, 2022, 18 patients, with a median age of 36.5 years, were enrolled; 10 were male, and 10 presented with advanced-stage disease. The most common hematologic toxicity was neutropenia (n = 9, 50%). Fifteen of the 18 participants completed treatment; 14 (93.3%) patients achieved a complete response, and one patient (6.7%) had a partial response. The OS and progression-free survival (PFS) at 12 months were 83% (95% CI, 68 to 100) and 67% (95% CI, 48 to 92), respectively. The OS and PFS at 24 months were 66% (95% CI, 47 to 92) and 67% (95% CI, 48 to 92), respectively.

Conclusion: As demonstrated in other parts of the world, sqR together with CHOP was safe, well-tolerated, and efficacious among Ugandan patients with DLBCL. The very high OS rates are nearly double those of historical controls and comparable with outcomes expected in resource-rich settings. This study demonstrated the feasibility, safety, and efficacy of sqR-CHOP, increased the research infrastructure in Uganda, and will improve care in other resource-limited settings.

Purpose: Although lung cancer is a major cause of cancer incidence and mortality worldwide, lung cancer studies in sub-Saharan Africa are scarce. Here, we present outputs from a designated lung cancer program in western Kenya, part of the Multi-National Lung Cancer Control Program, which focused on case finding, diagnosis, and treatment.

Methods: We retrospectively reviewed patients with pathologically confirmed non-small cell lung cancer (NSCLC) enrolled in this program at Moi Teaching and Referral Hospital from January 2018 to December 2022. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, and proportional hazards regression model.

Results: Two hundred forty-nine patients diagnosed with NSCLC were included with a median age at diagnosis of 61 (IQR, 52-70) years. Most patients were married (n = 177; 71%) and nonsmokers (n = 177; 71%) with 58 (23%) having received tuberculosis treatment and 93 (37%) having Eastern Cooperative Oncology Group (ECOG) performance status (PS) of $\ge$2. At diagnosis, adenocarcinoma was the prominent histology (n = 187; 75%) along with clinical stage IV (n = 195; 78% stage IV) or unstaged (n = 40; 16%) disease. Most patients received chemotherapy and radiotherapy (n = 176; 71%) with few palliative care referrals (n = 2; 0.8%). The median overall survival (OS) was only 3.7 months (IQR, 2.7-5.4). ECOG PS (3 or 4) and being unstaged were predictors of poor 1-year OS.

Conclusion: Patients with NSCLC enrolled in this program presented with advanced disease and poor survival. Despite a designated case finding effort, late diagnosis remained common and highlights a need for locally relevant interventions targeting community and provider education as well as innovative diagnostics that can improve early recognition of lung cancer. These interventions must also be paired with access to proven treatments including molecular therapies and palliative care which can extend lung cancer survival.

Purpose: Adjuvant anti-PD-1 (adj PD-1) antibodies are extensively used to improve survival in patients with resected melanoma. Clinical trials on adj PD-1 antibodies have revealed significant improvements in recurrence-free survival (RFS); however, few of these trials have included patients with acral melanoma (AM).

Methods: Clinical data were retrospectively collected from Japanese patients who underwent resection of stage III sole AM between 2014 and 2021. Survival outcomes, including RFS, distant metastasis-free survival (DMFS), and overall survival (OS), were compared between patients without adjuvant therapy (OBS group) and those receiving adj PD-1 group.

Results: This study included 139 patients (OBS: 79; adj PD-1: 60), with a median follow-up of 2.6 years. The baseline characteristics were comparable, except for age and nodal metastasis. No significant differences in survival were observed between the OBS and adj PD-1 groups (3-year RFS: 36.7% v 27.5%, P = .13; 3-year DMFS: 51.0% v 45.3%, P = .51; 3-year OS: 65.3% v 67.4%, P = .45). Multivariate analysis showed no survival benefit of adj PD-1 (RFS: hazard ratio [HR], 1.25, P = .29; DMFS: HR, 1.03, P = .89; and OS: HR, 0.69, P = .23). Each survival outcome after propensity score matching confirmed no significant difference between the matched OBS group (n = 52) and adj PD-1 group (n = 52; 3-year RFS: 34.3% v 25.9%, P = .22; 3-year DMFS: 45.6% v 46.5%, P = .85; 3-year OS: 60.7% v 68.9%, P = .29).

Conclusion: Adj PD-1 did not improve the prognosis in sole AM. However, further studies are essential to evaluate the efficacy of the adj anti-PD-1 antibody in AM.

Purpose: To evaluate the toxicity profile and efficacy of postoperative ultra-hypofractionated radiation therapy in elderly patients with breast cancer.

Materials and methods: This is a nonrandomized, single-center, prospective Phase II trial. Patients with breast cancer older than 65 years were treated with ultra-hypofractionated radiation therapy in 5 fractions of 5.7 Gy on alternate days in the breast or chest wall, or regional lymph nodes. The primary end point was acute toxicity.

Results: A total of 60 patients were analyzed, with a median follow-up of 42.5 months (range, 13.8-66.2). Most patients presented pathologic stage I (56.6%, n = 34) or stage II (33.3%, n = 20) disease. Regional lymph node irradiation was performed in 22% (n = 13) of patients. During treatment, 51% (n = 31) of patients experienced grade 1 or 2 acute toxicity, with no cases of grade 3 acute toxicity reported. Late toxicity included 1.7% (n = 1) of patients developing grade 3 fibrosis and 1.7% (n = 1) developing grade 3 pneumonitis. Regional lymph node irradiation was not associated with a statistically significant increase in toxicity risk (P = .194). Cosmesis evaluations revealed no significant changes when comparing pretreatment assessments with evaluations at 10 weeks (P = .223) and 26 weeks (P = .615) post-treatment. Quality of life was not adversely affected, regardless of whether regional lymph nodes were irradiated. Recurrence rates included two patients with both locoregional and distant recurrence and five patients with distant recurrence. The 3-year disease-free survival probability was 81.7%, and the 3-year overall survival probability was 86.7%.

Conclusion: This study demonstrates the safety of ultra-hypofractionated radiation therapy in terms of toxicity in patients with breast cancer. The findings for side effects, cosmesis, quality of life, and survival outcomes are consistent with those observed in moderately hypofractionated radiation therapy regimens, suggesting its use as a viable treatment option in this demographic.

Purpose: Non-small cell lung cancer (NSCLC) is often diagnosed at late stages, leading to escalated treatment expenses. This study aimed to elucidate the costs of lung cancer treatment in a private health care setting in Brazil.

Materials and methods: We conducted a retrospective cohort study, regarding costs, survival, and quality of care of stage IV NSCLC in a private health company in Brazil.

Results: A total of 819 individuals were included, with median age 64.9 years. With a 1-year follow-up, patients had a median of four hospital admissions, with a median length of stay in of 6.2 days. Survival rates were higher for patients treated with targeted therapy (hazard ratio [HR], 0.38 [95% CI, 0.25 to 0.56]), immunotherapy (HR, 0.52 [95% CI, 0.40 to 0.68]), or both treatments sequentially (0.41 [95% CI, 0.25 to 0.68]). Patients submitted to sequentially targeted therapy and immunotherapy had the higher total costs (mean, $172,828 USD) compared with patients treated with immunotherapy (mean, $138,125 USD), targeted therapy (mean, $117,068 USD), and only chemotherapy (mean, $47,625 USD). As expected, longer survival was translated into more third-line therapy (P < .001), and higher mean costs with cancer-related hospital admissions ($24,554 USD chemo, $31,835 USD immuno, $28,228 USD targeted, and $35,494 USD for both therapies). However, costs did not increase in proportion to the survival benefit. Despite longer survival, patients undergoing targeted therapy or immunotherapy had median number of hospital admissions and length of stay similar to those who underwent chemotherapy alone.

Conclusion: Higher survival rates and costs were found for patients exposed to modern treatments for advanced NSCLC. Cost-effectiveness thresholds definitions are warranted for managing costs, particularly in developing countries.

Purpose: Optimal survival outcomes of prostate cancer are best achieved through high-quality care for curable disease. In Nigeria, various barriers may impede the curative treatment of prostate cancer, yet their impact on care and patient outcomes remains anecdotal. This study assessed treatment quality, survival outcomes, and interhospital differences of these metrics among patients with clinically localized prostate cancer in Nigeria.

Methods: A retrospective study of patients with clinical stage T1-T3a, M0 prostate cancer at three tertiary hospitals in Nigeria over a 3-year period was conducted. Data on hospital sites, sociodemographics, clinicopathologic characteristics, quality metrics, imaging used, treatment, and survival status were collected. The primary end point was time from diagnosis to first treatment. Secondary end points were time from presentation to diagnosis, other prostate cancer quality metrics, all-cause survival, and interhospital differences in these metrics. Quality of diagnostics, treatments, and other outcomes were described and compared using Cox regression.

Results: This study included 110 patients with a median age of 67 years. Most (n = 66, 61%) had high-risk disease. The median time from tertiary hospital presentation to diagnosis was 31 days. Median time from diagnosis to first treatment of any type was 68 days, with radical radiotherapy was 117 days, and with radical prostatectomy was 104 days. Eighteen percent (n = 20) had guideline-concordant imaging for tumor staging, 67 patients (61%) received any treatment or active surveillance, and retention in care was 42%. Three-year all-cause survival was 41%. There was a significant difference in most quality metrics including guideline-concordant imaging and treatment across the hospital sites.

Conclusion: Time to treatment was delayed beyond international benchmarks; quality of staging, treatment, and care process were suboptimal; and survival was poor amid geographical disparities in care.

Purpose: Utilization of clinical research methodology as a means for improvement in pediatric cancer outcomes is well established. Toward achievement of its WHO-Global Initiative for Childhood Cancer (GICC) goals in Pakistan, the Pakistan Society of Pediatric Oncology (PSPO) has used this methodology to develop and implement standard-of-care (SOC) protocols nationally, with centralized research and data management support. This article describes the strategy for its implementation and provides a foundation for future advancements in cancer care in Pakistan.

Methods: The following steps were used to achieve the objectives: Central Support: A central PSPO office was established with minimal required staffing for provision of support to clinicians for protocol development and implementation and housing data and documents. Clinical protocols: multi-institutional teams, supported by central staff, developed SOC protocols on the basis of international evidence and local experience for six GICC target diagnoses. These went through an iterative consultation and revision process and were finally approved by the PSPO Board. Protocol implementation: case report forms and databases were developed using RedCap software and tested for functionality. Education and training were provided to institutional principal investigators and data entry personnel on the disease, protocol, use of RedCap, and data entry. Data quality maintenance: a system was established for ongoing data quality maintenance through central support and augmented by virtual and on-site audits. Where required, targeted training was provided. Interim analyses are being performed to assess data quality and early outcomes.

Results: Development and implementation of protocols occurred over 26 months. Each protocol is currently active in at least seven centers. Almost 2,000 patients have been enrolled. Interim analysis of ALL data shows 85% data accuracy.

Conclusion: Research infrastructure and capacity building for implementation of multi-institutional treatment protocols in low- and middle-income countries with modest resources is feasible.

Purpose: Excellent survival for advanced (stages II with high lactate dehydrogenase, III, and IV) pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) has been achieved with intensive regimens, but adoption in sub-Saharan Africa is limited by inadequate supportive care. We provide real-world data on treating advanced MB-NHL with high-dose methotrexate (HD-MTX; ≥1,000 mg/m²/cycle) where real-time serum MTX monitoring is unavailable.

Methods: We identified two cohorts-a retrospective (January 2017-December 2020) cohort treated with 1,000 or 3,000 mg/m²/cycle of HD-MTX and a prospective (July 2022-July 2023) cohort-with a modified LMB96 protocol containing 3,000 mg/m²/cycle of HD-MTX. All doses of HD-MTX were given over 3 hours. Estimates of 12-month event-free survival (EFS) and overall survival (OS) were calculated with abandonment as an event. Clinical toxicity data were available for the prospective cohort.

Results: The retrospective cohort had 108 patients who received HD-MTX 1,000 mg/m² (n = 98, 91%) or 3,000 mg/m² per cycle. The 12-month EFS and OS were 39% (95% CI, 30 to 50) and 54% (95% CI, 44 to 64), respectively. HD-MTX at 3,000 mg/m² had superior EFS: 69% (95% CI, 49 to 96) versus 33% (95% CI, 24 to 46), P = .004. The prospective cohort had 38 patients. Two ≥grade 3 mucositis, one acute kidney injury, and three treatment-related deaths (8%) occurred. Seven (18%) abandoned treatment. With a median follow-up of 14.5 months, 12-month EFS and OS were 45% (95% CI, 32 to 65) and 59% (95% CI, 45 to 79), respectively. Most relapses were stage IV: EFS 20% versus 51% (non-stage IV; P = .057). Severe malnutrition was associated with OS of 33% versus 58% (normal) or 76% (moderate; P = .055).

Conclusion: HD-MTX dosed at 3,000 mg/m²/cycle is feasible in low-resource settings where routine MTX monitoring is unavailable. Stage IV disease and severe malnutrition may contribute to poorer outcomes.