Cancer

Introduction A prostate‐specific antigen (PSA) level >0.5 ng/mL after 9 to 10 weeks of neoadjuvant androgen deprivation therapy and before radiation therapy (RT) was associated with an increased PSA‐failure risk; however, the impact on all‐cause mortality (ACM) risk after adjusting for serum testosterone level remains unknown. Methods From 2005 to 2015, 350 patients with localized, unfavorable‐risk prostate cancer (PC) were randomly assigned to receive androgen deprivation therapy and RT plus docetaxel vs standard of care (SOC) with androgen deprivation therapy and RT. Multivariable Cox regression analyses were used to assess whether a significant association existed between PSA (continuous and categorized as ≤0.5 vs > 0.5 ng/mL) measured at 9 to 10 weeks after randomization and ACM risk, adjusting for known PC prognostic factors and baseline testosterone level. Results After a median follow‐up of 10.23 years (interquartile range: 8.07–11.41), 85 patients died (25.30%), 41 from PC (48.24%). PSA level at 9 to 10 weeks after randomization was significantly associated with increased risk of ACM when analyzed as a continuous (adjusted hazard ratio, 1.16; 95% CI, 1.04–1.30; p = .008) or categorical covariate (>0.5 vs ≤ 0.5 ng/mL; adjusted hazard ratio, 1.88; 95% CI, 1.12–3.17; p = .02) after adjusting for covariates. Conclusions This study validates that a PSA level >0.5 ng/mL after neoadjuvant androgen deprivation therapy and before RT is prognostic and significantly associated with an increased ACM risk. Patients achieving this endpoint should be considered for enrollment in future randomized trials evaluating the impact of treatment escalation on ACM using a prerandomization stratification by age or validated comorbidity metrics.

In their recent work, Hogan and colleagues shed light on predictors of radiation recommendation, initiation, and completion in the United States across 3 million patients. Further work should use qualitative and intersectional lenses to examine the root causes of poor access to radiation and identify ways to intervene. Steps forward should be multidisciplinary in scope, approaching radiation access through research, clinical interventions, and national policy.

The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2014 for treatment of patients with polycythemia vera (PV) who have an inadequate response to or intolerance of hydroxyurea (HU). PV is a chronic myeloproliferative neoplasm defined by primary absolute erythrocytosis, bone marrow hypercellularity, and JAK mutations such as JAK2V617F. Patients with PV experience burdensome symptoms and are at risk of thromboembolic events, in particular those with resistance to or intolerance of initial treatments such as HU. Other risks for patients with PV include progression of disease to more aggressive forms with worse prognoses, such as myelofibrosis or blast‐phase myeloproliferative neoplasms. This review summarizes the efficacy and safety of ruxolitinib from key phase 2 and 3 trials (MAJIC‐PV, RESPONSE, RESPONSE‐2, RELIEF, and Ruxo‐BEAT), large real‐world studies, and a decade of postmarketing surveillance safety data. The authors focus on improved blood count control, rates of thromboembolic events, symptom improvement, and markers of disease modification such as reduction of JAK2V617F allele burden in patients treated with ruxolitinib. They also discuss the well‐characterized safety profile of ruxolitinib regarding hematologic and other adverse events of interest. In the 10 years since its approval, ruxolitinib remains a safe and effective standard‐of‐care treatment for PV. As the treatment landscape for PV continues to evolve in the coming years, the efficacy and safety profiles of ruxolitinib suggest it will remain a preferred treatment as monotherapy and as a potential backbone of future combination regimens.

Current US clinical practice guidelines for advanced prostate cancer management contain recommendations based on high‐level evidence from randomized controlled trials; however, these guidelines do not address the nuanced clinical questions that are unanswered by prospective trials but nonetheless encountered in day‐to‐day practice. To address these practical questions, the 2024 US Prostate Cancer Conference (USPCC 2024) was created to generate US‐focused expert clinical decision‐making guidance for circumstances in which level 1 evidence is lacking. At the second annual USPCC meeting (USPCC 2024), a multidisciplinary panel of experts convened to discuss ongoing clinical challenges related to 5 topic areas: biochemical recurrence; metastatic, castration‐resistant prostate cancer; poly [ADP‐ribose] polymerase inhibitors; prostate‐specific membrane antigen radioligand therapy; and metastatic, castration‐resistant prostate cancer. Through a modified Delphi process, 34 consensus recommendations were developed and are intended to provide clinicians who manage prostate cancer with guidance related to the implementation of novel treatments and technologies. In this report, the authors review the areas of consensus identified by the USPCC 2024 experts and evaluate ongoing unmet needs regarding translational application of the current clinical evidence.

Gender disparities in academic medicine persist despite gender parity among medical school graduates. Women remain underrepresented in higher academic ranks and leadership roles, with significant differences in retention, promotion, and compensation. In this scoping review, the authors explore the role of networking and social capital in exacerbating these disparities. The literature reviewed highlights the importance of networking in obtaining leadership roles, decreasing social isolation, and enhancing retention. Sponsorship, distinct from mentorship, is vital for career development and has a direct impact on professional growth. However, women are often under‐sponsored compared with men, limiting their access to influential networks. In addition, virtual networking platforms and women‐focused organizations offer promising alternatives to traditional, male‐dominated networking activities. Despite the progress made, informal networking practices and gender biases continue to exclude women from key opportunities. These findings underscore the need for targeted interventions aimed at enhancing the social capital of women in academic medicine to help close the gender gap. Proposed interventions prime for further evaluation include the implementation of formal sponsorship programs, the development of structured networking opportunities, and the promotion of women‐focused organizations.

Background The lifetime risk of pancreatic cancer in women with a germline mutation in BRCA1 and BRCA2 is not well established. In an international prospective cohort of female carriers of BRCA1 and BRCA2 mutations, the cumulative incidence of pancreatic cancer from age 40 until 80 years was estimated. Methods A total of 8295 women with a BRCA1 or BRCA2 mutation were followed for new cases of pancreatic cancer. Subjects were followed from the date of baseline questionnaire or age 40 years (whichever came last) until a new diagnosis of pancreatic cancer, death from another cause, or date of last follow‐up. Results Thirty‐four incident pancreatic cancer cases were identified in the cohort. The annual risk of pancreatic cancer between age 40 and 80 years was 0.04% for BRCA1 carriers and 0.09% for BRCA2 carriers. Via the Kaplan–Meier method, the cumulative incidence from age 40 to 80 years was 2.2% (95% CI, 1.1%–4.3%) for BRCA1 carriers and 2.7% (95% CI, 1.3%–5.4%) for BRCA2 carriers. Only two of the 34 cases reported a first‐degree relative with pancreatic cancer (hazard ratio, 4.75; 95% CI, 1.13–19.9; p = .03). Risk factors for pancreatic cancer included alcohol intake and a history of diabetes. The 5‐year survival rate for the 34 cases was 8.8%. Conclusions The lifetime risk of pancreatic cancer is approximately 2% in women with a BRCA1 mutation and 3% for women with a BRCA2 mutation. The poor survival in hereditary pancreatic cancer underscores the need for novel antitumoral strategies.

This editorial underscores the benefits of combining exercise, nutrition, and psychosocial support in bladder cancer care to enhance patients' quality of life and recovery outcomes. Evidence from multimodal interventions highlights the value of this approach, with telehealth emerging as a promising tool to address access barriers and support comprehensive care.

This editorial examines vascular endothelial growth facto and programmed cell death‐1 inhibition combinations in bone sarcomas, revealing limited efficacy in unselected patients. Future success in treating these challenging tumors requires better predictive biomarkers and more effective immunotherapy combinations.

Background Health care inequities have partially contributed to the existing racial gaps in health. Despite having lower incidence rates of breast cancer, Black women have a 41% higher mortality rate than White women. Black individuals remain underrepresented in research. Diversity in research is paramount to the improvement of clinical care practices and subgroup‐specific guidelines. Methods Black women from various community venues across geographic regions of the United States were invited via email, online fliers, social media platforms, and word of mouth to participate in focus groups. Six online focus groups of six to 10 Black women aged 25–65 years (N = 38) with and without a history of cancer were conducted with an in‐depth semistructured discussion guide. Results Most participants were college educated (32 of 38; 84.2%), aged 50 years or older (31 of 38; 81.6%), and had an annual income of $50,000 or more (26 of 38; 68.4%). Several barriers to research participation were identified. They included a lack of empathy and respect in health care settings, apprehension regarding the sharing of personal information, mistrust of medical research, and logistical/technical barriers. Alternatively, building individual and community trust and communicating the value of conducting research beneficial to the Black community were viewed as facilitators to research participation. Conclusions Successful engagement of Black women in research requires the acknowledgment and consideration of the numerous barriers that affect their ability to participate. Black women are more inclined to participate in research when the research team is knowledgeable, has experience within their communities, and engages trusted community partners. Additionally, the research must be meaningful and impactful to future generations of Black women.

Carpenter et al. add to the body of evidence demonstrating that irradiated head and neck cancer survivors are at high risk for carotid artery stenosis. In this editorial, the concept of screening for asymptomatic carotid artery stenosis in this subpopulation is explored.

Background The objective of this study was to assess patient‐reported outcomes (PROs), including health‐related quality of life (HRQoL) and anxiety and depression symptoms, and to identify associated variables in patients with tyrosine kinase inhibitor (TKI)‐resistant chronic myeloid leukemia (CML) in chronic‐phase (CP) or accelerated‐phase (AP) who were receiving olverembatinib. Methods Patients in multicenter studies were invited to complete the European Organization for Research and Treatment of Cancer Quality‐of‐Life Core 30 Questionnaire, the Self‐Rating Anxiety Scale, and the Self‐Rating Depression Scale at baseline and regularly during olverembatinib therapy. The time trends in PROs were estimated with a linear model using a generalized estimating equation based on an independent working correlation matrix. A generalized estimating equation model was used to assess the variables associated with PROs. Results In total, 146 patients with CML‐CP or CML‐AP were included in this study. Scores on seven items from the European Organization for Research and Treatment of Cancer Quality‐of‐Life Core 30 Questionnaire, including global health, physical functioning, emotional functioning, fatigue, dyspnea, diarrhea, and financial difficulties, improved significantly over time during olverembatinib therapy. In multivariate analysis, age younger than 40 years was significantly associated with greater improvement in social functioning (p = .033), and CML‐CP (vs. CML‐AP) was associated with greater improvements in dyspnea (p = .031) and diarrhea (p = .031) over time. Scores on the Self‐Rating Anxiety Scale and the Self‐Rating Depression Scale decreased significantly over time during olverembatinib treatment (p < .001). Conclusions The authors concluded that HRQoL significantly improved over time during olverembatinib therapy in heavily treated patients with TKI‐resistant CML, especially among those who were younger and those who had CML‐CP. Anxiety symptoms also significantly decreased over time.

Background All‐trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard‐risk acute promyelocytic leukemia (APL). Herein, the authors update their long‐term results with the regimen of ATO‐ATRA and gemtuzumab ozogamicin (GO) in standard‐risk and high‐risk APL. Methods This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m² and ATO 0.15 mg/kg daily. GO 6–9 mg/m² was added for high‐risk patients and for standard‐risk patients who developed leukocytosis >10 × 10⁹/L. Consolidation consisted of four courses of ATO‐ATRA, with GO for patients who had PML::RARA persistence. Results One hundred forty‐six patients (median age, 53.0 years; range, 19.3–83.9 years) were treated, including 106 patients (72.6%) with standard‐risk APL and 40 (27.4%) with high‐risk APL. GO was administered to 68 standard‐risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%–98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow‐up of 61.8 months (95% CI, 4.7–128.4 months), the 5‐year event‐free survival, disease‐free survival, and overall survival rates were 92.4% (95% CI, 87.9%–97.1%), 93.6% (95% CI, 89.5%–97.8%), and 93.1% (95% CI, 88.9%–97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno‐occlusive disease. Conclusions The combination of ATO‐ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).

Background CALGB 30610 trial demonstrated that once daily thoracic radiotherapy (TRT) was not superior compared to standard twice daily TRT, in patients with limited stage small cell lung cancer. Quality of life outcomes may help oncologists decide the best treatment approach. Methods A total of 417 patients on CALGB 30610 participated in the quality‐of‐life substudy (CALGB 70702), which included the FACT Trial Outcome Index‐Lung Cancer (FACT‐L TOI), FACT‐Esophageal Cancer (FACT‐E) Eating and Swallowing Indices, ECOG Acute Esophagitis Scale, Hospital Anxiety and Depression Scale (HADS), difficulty swallowing, EQ‐5D, and treatment convenience assessment at baseline, 3, 5, 7, 12, 26, and 52 weeks after starting TRT. Primary end points included FACT‐L TOI and FACT‐E at 12 weeks. Mean changes from baseline were compared between arms using general linear mixed models. Results FACT‐L worsening was more in the twice daily arm at week 3 (–1.0 vs. –7.0). FACT‐L TOI worsening was less at week 3 (–2.9 vs. –7.6) and greater at week 12 (–7.6 vs. –2.8) in the once daily arm. The once daily arm had a lower EQ‐5D index worsening at 3 weeks (0.01 vs. –0.02). Increase in acute esophagitis score (1.06 vs. 2.89; p < .001) and difficulty swallowing (0.39 vs. 1.14) were greater in the twice daily arm at week 3. A total of 74.5% of patients on the once daily arm felt that treatment was convenient, compared to 67% of patients in the twice daily arm (p = .03). Conclusions The once daily arm had better quality‐of‐life scores earlier during treatment and was perceived to be more convenient.

Retroperitoneal sarcoma is a complex entity that requires specialized surgical management. Three‐dimensional printing technology may represent a valuable adjunctive tool for the preoperative assessment and surgical planning of retroperitoneal sarcoma.

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. This issue features Dr Quynh‐Thu Le, who confronts the difficult challenges of improving the efficacy and safety of radiation therapy in the treatment of head and neck cancers. In addition, molecularly guided therapy improves survival outcomes for patients with a cancer of unknown primary, and annual screening mammography lowers the risk of late‐stage cancer.

This systematic review describes difference in patient‐relevant outcomes between comprehensive cancers (CCCs) versus non‐CCCs. Studies were identified in PubMed, Cochrane CENTRAL, Epistemonikos, and gray literature from January 2002 to May 2024. Data were extracted and appraised by two authors. Results were narratively synthesized, and meta‐analyzed where appropriate. Of 2272 records screened, 36 observational studies were included, predominantly from the United States, and focused on adults with solid cancers. Compared to non‐CCCs, studies consistently or predominantly reported superior outcomes at CCCs relating to mortality and survival, quality of peri‐ and postoperative care, rates of cancer recurrence or progression, and impact on symptoms and health‐related quality of life. Meta‐analysis showed a significantly lower overall mortality risk of 23% in CCCs compared to non‐CCCs (hazard ratio, 0.77; 95% confidence interval, 0.74–0.81, p < .001), with medium heterogeneity (I² = 64.61%; Q‐test = 36.29, p < .01) observed between the studies. Studies reporting on health equity and costs outcomes consistently or predominantly favored non‐CCCs over CCCs. Mixed results were reported for outcomes relating to time to care, palliative and end‐of‐life care, and health care utilization. The literature reports CCCs are associated with superior outcomes in many areas, especially around mortality and survival. Greater focus is needed to explore outcomes that are important to people with cancer including health‐related quality of life, symptoms, and treatment experience, and economic evaluation. Rather than aiming for superior outcomes, CCCs should be striving to enable equitable, high value, patient‐centered outcomes for all people affected by cancer.

Generative artificial intelligence offers promising avenues for patient education, but its current limitations necessitate a cautious and well informed approach to use. The health care system must adapt to emerging technologies while also striving to deliver timely and patient friendly communication and build trust with the populations they intend to serve.

Plain Language Summary We commend the American Society of Clinical Oncology for their sweeping recommendations and advocacy for integrated palliative care as part of oncologic care. The literature that exists is heterogeneous and at times difficult to interpret, and the panel has clearly described their systemic review process and subsequent rationale for their recommendations. Although we agree with the overall recommendations, there are significant practical limitations to their application that renders them aspirational. We worry that the guidelines may be impossible for most programs to fully achieve due to a variety of factors including specialty palliative care workforce shortages, limited health care system resource allocation to integrate palliative care widely in cancer care, and lack of financial support for the research necessary to better answer outstanding clinical and implementation questions. We outline briefly some practical ways in which these recommendations can be applied by existing cancer centers and health care systems. Ultimately, both financial and quality incentives will be necessary to push forward the expansion and integration of palliative care within our national health care system as a whole.

Background Cancer remains a significant challenge for health care systems, despite notable progress in the field. These advancements have significant financial implications that disproportionately affect low‐income countries. This review article aims to explore the present state of drug development, assessing the availability of drugs in different income countries, and proposing potential solutions to address the inequality in access to new cancer treatments. Methods A search was conducted on MEDLINE and PubMed on October 2, 2023 and updated on December 14, 2023, limited to English language articles. Results There is a projected rise in cancer cases worldwide, particularly in low‐income countries where most cancer‐related deaths are expected. Although the approval rate of cancer treatments has risen, their excessive cost and lack of affordability pose significant barriers to widespread access. Disparities in the costs of crucial cancer medications are influenced by geographic location and procurement connections. Potential solutions to address the inequity in drug distribution include sharing production secrets, implementing price discrimination, international funding, improved primary health care measures, and the implementation of cost‐effective screening methods. Conclusion Preventing, screening for, and treating cancer should be a global priority with minimal differences in access to therapy among various countries.

Background One third of adults with cancer suffer from common mental disorders in addition to their malignant disease. However, it is unknown whether this proportion is the same in patients who have brain tumors and which factors modulate the risk for psychiatric comorbidity. Methods In a multicenter study, patients with high‐grade glioma at 13 neurooncology clinics were enrolled consecutively and interviewed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID) to diagnose common mental disorders. Predictors of psychiatric comorbidity were investigated using binary logistic regression. Results Six hundred ninety‐one patients were interviewed. The proportion of patients who had mental disorders was 31% (95% confidence interval [CI], 28%–35%). There was evidence for an association of psychiatric comorbidity with the following factors: younger age (odds ratio [OR], 1.9; 95% CI, 1.1–3.4; p = .04), stable disease versus complete remission (OR, 1.7; 95% CI, 1.1–2.8; p = .04), lower income (OR, 1.7; 95% CI, 1.0–2.8; p = .04), living alone (OR, 1.6; 95% CI, 1.0–2.6; p = .05), fatigue (OR, 1.6; 95% CI, 1.1–2.4; p = .03), and impaired cognitive functioning (OR, 2.3; 95% CI, 1.5–3.6; p < .01). There was no evidence for independent effects of gender, histology, affected lobe, time since diagnosis, or employment status. Conclusions Approximately one third of adult patients with high‐grade glioma may suffer from a clinically relevant common mental disorder, without notable disparity between the genders. In particular, clinicians should pay attention to possible comorbidities for cases in which patients exhibit compromised subjective cognitive function, are younger than 50 years, maintain a state of stable disease, or live alone.

Background Improved breast cancer treatment has lengthened survival but also has long‐term impacts. Lymphedema and peripheral neuropathy are treatment‐related sequelae that extend into survivorship. Co‐occurrence of these conditions may further impair functional well‐being. Few studies have estimated the burden of these conditions among diverse survivors. Methods Carolina Breast Cancer Study Phase 3 enrolled survivors diagnosed between 2008 and 2013 in North Carolina. Black and younger women (aged <50 years at diagnosis) were oversampled. With the use of ≥10 years of follow‐up data, the prevalence of persistent lymphedema, peripheral neuropathy, and their co‐occurrence was assessed. Prevalence differences (PDs) and 95% confidence intervals (CIs) were assessed according to patient and disease characteristics. Results A total of 1688 survivors were included, with an average of 11.1 years (SD, 0.6) postdiagnosis. The prevalence of persistent lymphedema, peripheral neuropathy, and their co‐occurrence was 18.7%, 27.7%, and 8.8%, respectively. Lymphedema was higher among those receiving a mastectomy and with >5 lymph nodes removed, and peripheral neuropathy was higher among women treated with taxane‐based chemotherapy. Co‐occurrence was higher among women with >5 lymph nodes removed (vs. <5; PD, 5.4; 95% CI, 2.1 to 8.8) and those treated with taxane‐based chemotherapy (vs. no chemotherapy; PD, 6.8; 95% CI, 3.9 to 9.7). The burden of lymphedema (PD, 2.7; 95% CI, 0.9 to 6.3) and peripheral neuropathy (PD, 5.8; 95% CI, 1.7 to 9.9) was higher among Black than White women. The prevalence of lymphedema (PD, 1.8; 95% CI, −1.5 to 5.1) and peripheral neuropathy (PD, 4.6; 95% CI, 0.8 to 8.4) was elevated among younger compared to older women. Conclusions Lymphedema and peripheral neuropathy affect a substantial proportion of survivors. Interventions are needed to reduce this burden.

There has been a paradigm shift in the treatment strategy for patients with desmoid tumor toward less invasive management using systemic therapies. In addition to older drugs, such as conventional chemotherapy and tyrosine kinase inhibitors, the newest class of medical agents—the gamma secretase inhibitors—have been included in the treatment armamentarium for patients with desmoid tumor, as nicely depicted in the latest consensus guideline from The Desmoid Tumor Working Group.