International Recommendations for Screening and Preventative Practices for Long-Term Survivors of Transplantation and Cellular Therapy: A 2023 Update.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the number of HCTs performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pretransplantation, peritransplantation, and post-transplantation exposures and other underlying risk factors. Guidelines for screening and preventive practices for HCT survivors were originally published in 2006 and then updated in 2012. An international group of experts was convened to review the contemporary literature and update the recommendations while considering the changing practices of HCT and cellular therapy. This review provides updated pediatric and adult survivorship guidelines for HCT and cellular therapy. The contributory role of chronic graft-versus-host disease (cGVHD) to the development of late effects is discussed, but cGVHD management is not covered in detail. These guidelines emphasize the special needs of patients with distinct underlying HCT indications or comorbidities (eg, hemoglobinopathies, older adults) but do not replace more detailed group-, disease-, or condition-specific guidelines. Although these recommendations should be applicable to the vast majority of HCT recipients, resource constraints may limit their implementation in some settings.

Survival differences in non-seminoma testis cancer patients according to race/ethnicity.

BACKGROUND: Historic evidence suggests that non-Caucasian race/ethnicity predisposes to higher testis cancer-specific mortality (CSM) in non-seminoma. However, it is unknown, whether higher CSM in non-Caucasians applies to Hispanics or Asians or African-Americans, or all of the above groups. In contemporary patients, we tested whether CSM is higher in these select non-Caucasian groups than in Caucasians, in overall and in stage-specific comparisons: stage I vs. stage II vs. stage III. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2004 -2019) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of race/ethnicity on CSM after stratification for stage (I vs. II vs. III) and adjustment for prognosis groups in stage III. RESULTS: In all 13,515 non-seminoma patients, CSM in non-Caucasians was invariably higher than in Caucasians. In stage-specific analyses, race/ethnicity represented an independent predictor of CSM in Hispanics in stage I (HR 1.8, p = 0.004), stage II (HR 2.2, p = 0.007) and stage III (HR 1.4, p < 0.001); in African-Americans in stage I (HR 3.2; p = 0.007) and stage III (HR 1.5; p = 0.042); and in Asians in only stage III (HR 1.6, p = 0.01). CONCLUSIONS: In general, CSM is higher in non-Caucasian non-seminoma patients. However, the CSM increase differs according to non-Caucasian race/ethnicity groups. Specifically, higher CSM applies to all stages of non-seminoma in Hispanics, to stages I and III in African-Americans and only to stage III in Asians. These differences are important for individual patient management, as well as for design of prospective trials.

Does Failure to Rescue Drive Race/Ethnicity-based Disparities in Survival After Heart Transplantation?

OBJECTIVE: The objective was to assess whether race/ethnicity is an independent predictor of failure to rescue (FTR) after orthotopic heart transplantation (OHT). SUMMARY BACKGROUND DATA: Outcomes following OHT vary by patient level factors; for example, non-White patients have worse outcomes than White patients after OHT. Failure to rescue is an important factor associated with cardiac surgery outcomes, but its relationship to demographic factors is unknown. METHODS: Using the United Network for Organ Sharing database, we included all adult patients who underwent primary isolated OHT between 1/1/2006 snd 6/30/2021. FTR was defined as the inability to prevent mortality after at least one of the UNOS-designated postoperative complications. Donor, recipient, and transplant characteristics, including complications and FTR, were compared across race/ethnicity. Logistic regression models were created to identify factors associated with complications and FTR. Kaplan Meier and adjusted Cox proportional hazards models evaluated the association between race/ethnicity and posttransplant survival. RESULTS: There were 33,244 adult, isolated heart transplant recipients included: the distribution of race/ethnicity was 66% (n=21,937) White, 21.2% (7,062) Black, 8.3% (2,768) Hispanic, and 3.3% (1,096) Asian. The frequency of complications and FTR differed significantly by race/ethnicity. After adjustment, Hispanic recipients were more likely to experience FTR than White recipients (OR 1.327, 95% CI[1.075-1.639], P =0.02). Black recipients had lower 5-year survival compared with other races/ethnicities (HR 1.276, 95% CI[1.207-1.348], P <0.0001). CONCLUSIONS: In the US, Black recipients have an increased risk of mortality after OHT compared with White recipients, without associated differences in FTR. In contrast, Hispanic recipients have an increased likelihood of FTR, but no significant mortality difference compared with White recipients. These findings highlight the need for tailored approaches to addressing race/ethnicity-based health inequities in the practice of heart transplantation.

El dilema clínico frente a los pacientes con ergometría positiva y prueba de perfusión miocárdica con SPECT normal / The clinical dilemma facing patients with positive stress test and normal SPECT myocardial perfusion imaging

La evaluación de la perfusión miocárdica con SPECT combina una prueba de esfuerzo (ergometría o estrés farmacológico) junto a imágenes de perfusión con radioisótopos. Este estudio es útil para establecer el diagnóstico de enfermedad arterial coronaria, estratificar el riesgo de infarto y tomar decisiones terapéuticas. Un resultado normal aporta un alto valor predictivo negativo, es decir, una muy baja probabilidad de que el paciente presente eventos cardiovasculares. El hallazgo de signos de isquemia en la ergometría podría poner en jaque el valor predictivo negativo de una perfusión normal. En presencia de este resultado, el paso siguiente es evaluar los predictores de riesgo en la ergometría, el riesgo propio del paciente en función de los antecedentes clínicos y el puntaje cálcico coronario, cuando este se encuentra disponible. Ante la presencia concomitante de otros marcadores de riesgo se sugiere completar la evaluación con un estudio anatómico.El uso de nuevas tecnologías podría mejorar la precisión en la predicción de eventos. (AU)

Assessment of myocardial perfusion with SPECT combines a stress test (ergometry or pharmacological stress) with radioisotope perfusion imaging. This test is helpful to diagnose coronary artery disease, stratify the risk of heart attack, and make therapeutic decisions. A normal result provides a high negative predictive value; therefore, the probability of cardiovascular events is very low. Signs of ischemia on an ergometry could jeopardize the negative predictive value of normal perfusion. In this clinical setting, the next step is to evaluate the risk predictors in the stress test, the individual risk based on the clinical history, and the coronary calcium score when available. Given the simultaneous presence of other risk markers,completing the evaluation with an anatomical study is suggested. The use of new technologies could improve the accuracy of event prediction. (AU)

Clinical profiles in multiple myeloma patients with extreme survivals: a study from a National Medical Center in China.

OBJECTIVES: The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice. METHODS: This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months. RESULTS: CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively. CONCLUSIONS: The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

Nutritional Care Guide for Pediatric Cancer

This guide has been developed as part of the World Health Organization's Global Initiative for Childhood Cancer, known as "Cure All Americas," with the primary purpose of alleviating the challenges faced by pediatric oncology patients. Its mission is to ensure that these young patients enjoy a full and high-quality life while receiving comprehensive nutritional care throughout the course of their illness. In Latin America and the Caribbean, the prevalence of malnutrition in children and adolescents diagnosed with cancer is alarmingly high at the time of diagnosis. Malnutrition not only undermines recovery prospects but also deteriorates the quality of life for these patients. This guide is aimed at the multidisciplinary pediatric oncology care team, including medical professionals, nutritionists, nurses, and other specialists. Drawing from the most robust scientific evidence, it addresses essential aspects such as nutritional screening, risk assessment, nutritional care planning, and the promotion of a healthy lifestyle for cancer survivors. It is worth emphasizing that this guide represents a milestone in the battle against childhood cancer in the region, as it seeks to significantly enhance the quality of life for pediatric patients affected by this disease. By providing healthcare professionals with the necessary tools and knowledge to address malnutrition and its impact on cancer treatment, we are taking a significant step towards a more hopeful future for the children and adolescents facing this challenging battle. The guide is an essential resource that offers comprehensive support in addressing the nutritional and health challenges of these young patients, thereby contributing to more effective treatment and a more promising prognosis.

Acting on past lessons and learning new ones.

eLife has published a special issue containing articles that examine how cancer prevention, control, care and survivorship were impacted by the COVID-19 pandemic.

[An enjoyable 23-year career as a hematologist in metropolitan emergency hospitals, a researcher of post-transplant survivorship, and a community hematologist-oncologist].

I would like to express my sincere gratitude to be given such an honorable opportunity. I am more than happy to share my personal experience as one example of the diversity of women in hematology. After graduating from Tohoku University, I began my residency training at Japanese Red Cross Musashino Hospital and Tokyo Metropolitan Bokutoh Hospital, which are extremely busy designated hospitals in Tokyo. Both had highly active emergency care centers, and I believe that the rigorous training I received there not only honed my basic patient care skills, but also increased my physical and mental strength. Since I referred many patients to National Cancer Center Hospital, I found it amusing that Dr. Fukuda recruited me based on the recommendation of those patients. I was so fortunate to have many opportunities to contribute as a primary investigator in meaningful nationwide clinical studies. At present, I appreciate my country life as a community hematologist-oncologist. I also did not expect that I would have continuing opportunities to collaborate with researchers nationwide thanks to rapid progress in remote communications, and nothing would make me happier than to continue participating in projects on cancer survivorship.

Post-Operative Care of the Cancer Patient: Emphasis on Functional Recovery, Rapid Rescue, and Survivorship.

A cancer diagnosis and its subsequent treatments are life-changing events, impacting the patient and their family. Treatment options available for cancer care are developing at pace, with more patients now able to achieve a cancer cure. This is achieved through the development of novel cancer treatments, surgery, and modern imaging, but also as a result of better understanding treatment/surgical trauma, rescue after complications, perioperative care, and innovative interventions like pre-habilitation, enhanced recovery, and enhanced post-operative care. With more patients living with and beyond cancer, the role of survivorship and quality of life after cancer treatment is gaining importance. The impact cancer treatments can have on patients vary, and the "scars" treatments leave are not always visible. To adequately support patients through their cancer journeys, we need to look past the short-term interactions they have with medical professionals and encourage them to consider their lives after cancer, which often is not a reflection of life before a cancer diagnosis.

Assessing the Efficacy of a 28-Day Comprehensive Online Prostate Cancer Patient Empowerment Program (PC-PEP) in Facilitating Engagement of Prostate Cancer Patients in Their Survivorship Care: A Qualitative Study.

A 28-day Prostate Cancer-Patient Empowerment Program (PC-PEP) developed through patient engagement was successful at promoting mental and physical health. Thirty prostate cancer patients from Halifax, Canada participated in the 28-day PC-PEP intervention in early 2019. PC-PEP encompassed daily patient education and empowerment videos, prescribed physical activities (including pelvic floor exercises), a mostly plant-based diet, stress reduction techniques, intimacy education, social connection, and support. Quantitative exit surveys and semi-structured interviews (conducted in focus groups of ten) were used to assess perceived factors that facilitated or impeded adherence to the program. The program received high praise from the patients and was deemed extremely useful by the participating men, who rated it 9 out of 10. Patients expressed that the multifaceted, online, home-based nature of the program helped them adhere to it better than they would have had to a single or less comprehensive intervention. Feedback from the participants indicated that the program, when viewed as a whole, was perceived as greater than the sum of its individual parts. Furthermore, the program addressed various issues, including emotional vulnerability and distress, physical fitness, urinary incontinence, challenges in expressing emotions, perceived lack of control over healthcare decisions, emotional fragility, and hesitancy to discuss prostate cancer-related matters in social settings. Patients highly (9.6/10) endorsed integrating the program into the standard care regimen from the very beginning of diagnosis. However, challenges such as work commitments were noted. Patients' high endorsement of PC-PEP suggests that its implementation into the standard of care from day one of diagnosis may be warranted.

Healthcare providers' perceptions about the unmet needs of their patients with cancer across healthcare systems: results of the International Psycho-Oncology Society survivorship survey.

OBJECTIVE: Systematic understanding of patients' unmet needs is essential for providing effective supportive care. This study sought to compare the unmet needs of patients with cancer identified by health care providers (HCPs) among four major healthcare systems. METHODS: HCPs (n = 247) participated in the International Psycho-Oncology Society (IPOS) Survivorship Online Survey, evaluating their patients' unmet needs. The country of HCPs was grouped into four major healthcare systems: Beveridge model, Bismarck model, National Health Insurance model, and out-of-pocket model. RESULTS: Most HCPs were from countries with the Bismarck model. Substantial levels (> 50%) of unmet needs in all domains are reported across the four healthcare systems. Pediatric patients/survivors living in countries under out-of-pocket healthcare model were evaluated to have less unmet needs for managing decline in physical or cognitive functioning and insomnia/sleep difficulty/fatigue, than those in countries under Beveridge, Bismarck, and National Health Insurance models. Moreover, middle-aged patients/survivors under Beveridge and National Health Insurance models were likely to have greater unmet needs for dealing with cancer-related financial concerns than those under Bismarck model. CONCLUSION: This study provides valuable insights into the unmet needs of patients with cancer in different healthcare systems, highlighting the significance of targeted interventions to address the unique needs of patients across diverse healthcare systems. Further investigation is warranted to identify the system factors associated with patients' unmet needs, enabling the development of effective healthcare policies and interventions to comprehensively address the multifaceted needs of patients with cancer.

Geometric graph neural networks on multi-omics data to predict cancer survival outcomes.

The advance of sequencing technologies has enabled a thorough molecular characterization of the genome in human cancers. To improve patient prognosis predictions and subsequent treatment strategies, it is imperative to develop advanced computational methods to analyze large-scale, high-dimensional genomic data. However, traditional machine learning methods face a challenge in handling the high-dimensional, low-sample size problem that is shown in most genomic data sets. To address this, our group has developed geometric network analysis techniques on multi-omics data in connection with prior biological knowledge derived from protein-protein interactions (PPIs) or pathways. Geometric features obtained from the genomic network, such as Ollivier-Ricci curvature and the invariant measure of the associated Markov chain, have been shown to be predictive of survival outcomes in various cancers. In this study, we propose a novel supervised deep learning method called geometric graph neural network (GGNN) that incorporates such geometric features into deep learning for enhanced predictive power and interpretability. More specifically, we utilize a state-of-the-art graph neural network with sparse connections between the hidden layers based on known biology of the PPI network and pathway information. Geometric features along with multi-omics data are then incorporated into the corresponding layers. The proposed approach utilizes a local-global principle in such a manner that highly predictive features are selected at the front layers and fed directly to the last layer for multivariable Cox proportional-hazards regression modeling. The method was applied to multi-omics data from the CoMMpass study of multiple myeloma and ten major cancers in The Cancer Genome Atlas (TCGA). In most experiments, our method showed superior predictive performance compared to other alternative methods.

[Clinical study of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of FLT3-ITD(+) acute myeloid leukemia with normal karyotype].

Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.

The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers.

PURPOSE: It is known that the RAS and BRAF mutations are predictive for targeted therapies in treating metastatic colon cancer and negatively affect the prognosis of the disease. However, there are limited studies in early-stage colon cancer about the relationship of this mutational condition with the prognosis and relapse pattern of the disease. In this study, we evaluated the effects of mutational status on the clinical pattern of recurrence and survival in early-stage colon cancer in addition to classical risk factors. METHODS: Patients with early-stage colon cancer at the first time of diagnosis and developing recurrence or metastasis on following up were included in this study. Patients were divided into two groups according to the at the time of relapse RAS/BRAF mutation status: mutant or non-mutant/wild types. Then, mutation analysis was performed again from the early-stage tissue of the patients if available. The relationship between early-stage mutation status and progression-free survival (PFS), overall survival (OS), and relapse pattern was analyzed. RESULTS: The number of patients with mutant and non-mutations in the early stage was 39 and 40, respectively. Mutant and non-mutant patients with stage 3 disease were similar (69% and 70%, respectively). OS (47.27 months vs. 67.53 months; p = 0.02) and PFS (25.12 vs. 38.13 months; p = 0.049) were statistically significantly lower in mutant patients, respectively. Most patients had distant metastases on both sides at recurrence (61.5% vs. 62.5%, respectively). There was no significant difference between mutant and non-mutant patients regarding distant metastasis and local recurrence rates (p = 0.657). A discordance of 11.4% between early-stage and late-stage tissue mutation status. CONCLUSION: The presence of mutation in early-stage colon cancer is associated with shorter OS and PFS. The mutational status did not have a significant effect on the recurrence pattern. Because of the discordance of early-stage and late-stage mutational status, it is recommended to perform mutation analysis from tissue at relapse.