Synchronous or metachronous breast and colorectal cancers in younger-than-average-age patients: a case series.

BACKGROUND: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. MATERIALS AND METHODS: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. RESULTS: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. CONCLUSION: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.

For the Long Haul: Management of Long-Term Survivors after Melanoma Systemic Therapy.

PURPOSE OF REVIEW: This review summarizes the latest advancements in survivorship care for patients with advanced melanoma who received systemic therapy and emphasizes the areas where more research is needed. RECENT FINDINGS: Over the last decade there have been remarkable advances in the treatment of advanced and metastatic melanoma. Due to these novel treatments, including several immune checkpoint inhibitors and tyrosine kinase inhibitors, there are and will continue to be increasing numbers of long-term melanoma survivors who have been treated with systemic therapy. These patients will navigate new challenges are they are essentially among the first long term survivors after these novel therapies. Survivorship care focuses on improving the health-related quality of life of patients including the physical, emotional, social and functional effects of cancer that begin at diagnosis and continue through the end of life. Survivorship also includes screening for cancer recurrence and second cancers. As the number of melanoma survivors who received systemic therapy continues to grow, the survivorship care plan will become increasingly important for optimal care of patients even after their cancer treatments. Understanding the many domains of survivorship care for this group of patients is imperative for their care now and to identify unmet needs for future research.

Antibody-drug conjugates as targeted therapy for treating gynecologic cancers: update 2025.

PURPOSE OF REVIEW: Provide the most up-to-date information on the dynamic landscape of antibody-drug conjugates (ADCs) in gynecologic cancers. We discuss the latest research that supports the approved ADCs and outline the ongoing trials and preliminary results that may lead to ADC approvals in the future. Current gaps in knowledge and areas for future research are discussed. RECENT FINDINGS: ADCs are rapidly changing the landscape of gynecologic cancer care. Three ADCs are currently FDA approved and used routinely in clinical practice, with many more currently in clinical development. The most common ADC target is folate receptor alpha of which there are 8 different folate receptor targeting ADCs in development. Other targets under investigation include trophoblast cell surface antigen-2 (Trop-2), claudin-6 (CLDN6), cadherin-6 (CDH6), nectin-4, HER-2 and B7-H4. ADCs can cause new and unique adverse effects, including ocular toxicities and interstitial lung disease. SUMMARY: ADCs offer the opportunity for a more effective and personalized treatment approach for gynecologic cancer patients. Side effects must be closely monitored, and preventive measures must be followed to maximize benefit and minimize toxicity. A better understanding of the role of target proteins as biomarkers to predict response to ADCs will be critical for successful clinical implementation of ADCs and further research in this area is necessary.

Evaluating Survival After Hospitalization Due to Immune-Related Adverse Events From Checkpoint Inhibitors.

BACKGROUND: As immune checkpoint inhibitors (CPI) are increasingly approved for cancer treatment, hospitalizations related to severe immune-related adverse events (irAE) will increase. Here, we identify patients hospitalized due to irAEs and describe survival outcomes across irAE, CPI, and cancer type. METHODS: We identified patients hospitalized at our institution from January 2012 to December 2020 due to irAEs. Survival was analyzed using Kaplan-Meier survival curves with log-rank tests. RESULTS: Of 3137 patients treated with CPIs, 114 (3.6%) were hospitalized for irAEs, resulting in 124 hospitalizations. Gastrointestinal (GI)/hepatic, endocrine, and pulmonary irAEs were the most common causes of irAE-related hospitalization. After CPI initiation, the average time to hospitalization was 141 days. Median survival from hospital admission was 980 days. Patients hospitalized due to GI/hepatic and endocrine irAEs had longer median survival than patients with pulmonary irAEs (795 and 949 days vs. 83 days [P < .001]). Patients with melanoma and renal cell carcinoma had longer median survival than patients with lung cancer (2792 days and not reached vs. 159 days [P < .001]). There was longer median survival in the combination group compared to the PD-(L)1 group (1471 vs. 529 days [P = .04]). CONCLUSIONS: As CPI use increases, irAE-related hospitalizations will as well. These findings suggest that among patients hospitalized for irAEs, survival differs by irAE and cancer type, with worse survival for patients with irAE pneumonitis or lung cancer. This real-world data contributes to research pertaining to hospitalization due to severe irAEs, which may inform patient counseling and treatment decision-making.

National experience with living donor liver transplantation for hepatocellular carcinoma.

Living donor liver transplantation (LDLT) is an attractive option to decrease waitlist dropout, particularly for patients with hepatocellular carcinoma (HCC) who face lengthening waiting times. Using the United Network for Organ Sharing (UNOS) national database, trends in LDLT utilization for patients with HCC were evaluated, and post-LT outcomes for LDLT versus deceased donor liver transplantation (DDLT) were compared. From 1998 to 2018, LT was performed in 20,161 patients with HCC including 726 (3.6%) who received LDLT. The highest LDLT utilization was prior to the 2002 HCC Model for End-Stage Liver Disease (MELD) exception policy (17.5%) and dropped thereafter (3.1%) with a slight increase following the 6-month wait policy in 2015 (3.8%). LDLT was more common in patients from long-wait UNOS regions with blood type O, in those with larger total tumor diameter (2.3 vs. 2.1 cm, p = 0.02), and higher alpha-fetoprotein at LT (11.5 vs. 9.0 ng/ml, p = 0.04). The 5-year post-LT survival (LDLT 77% vs. DDLT 75%), graft survival (72% vs. 72%), and HCC recurrence (11% vs. 13%) were similar between groups (all p > 0.20). In conclusion, LDLT utilization for HCC has remained low since 2002 with only a slight increase after the 6-month wait policy introduction in 2015. Given the excellent post-LT survival, LDLT appears to be an underutilized but valuable option for patients with HCC, especially those at high risk for waitlist dropout.

Donation After Circulatory Death Is Associated With Similar Posttransplant Survival in All but the Highest-Risk Hepatocellular Carcinoma Patients.

Liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) receive a higher proportion of livers from donation after circulatory death (DCD) donors compared with non-HCC etiologies. Nevertheless, data on outcomes in patients with HCC receiving DCD grafts are limited. We evaluated the influence of DCD livers on post-LT outcome among HCC patients. We identified 7563 patients in the United Network for Organ Sharing (UNOS) database who underwent LT with Model for End-Stage Liver Disease score exceptions from 2012 to 2016, including 567 (7.5%) who received a DCD donor organ and 6996 (92.5%) who received a donation after brain death (DBD) donor organ. Kaplan-Meier probabilities of post-LT HCC recurrence at 3 years were 7.6% for DCD and 6.4% for DBD recipients (P = 0.67) and post-LT survival at 3 years was 81.1% versus 85.5%, respectively (P = 0.008). On multivariate analysis, DCD donor (hazard ratio, 1.38; P = 0.005) was an independent predictor of post-LT mortality. However, a survival difference after LT was only observed in subgroups at higher risk for HCC recurrence including Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score ≥4 (DCD 57.0% versus DBD 72.6%; P = 0.02), alpha-fetoprotein (AFP) ≥100 (60.1% versus 76.9%; P = 0.049), and multiple viable tumors on last imaging before LT (69.9% versus 83.1%; P = 0.002). In this analysis of HCC patients receiving DCD versus DBD livers in the UNOS database, we found that patients with a low-to-moderate risk of HCC recurrence (80%-90% of the DCD cohort) had equivalent survival regardless of donor type. It appears that DCD donation can best be used to increase the donor pool for HCC patients with decompensated cirrhosis or partial response/stable disease after locoregional therapy with AFP at LT <100 ng/mL.

The radiologist's role in a multidisciplinary approach to cancer in pregnancy.

Pregnancy-associated cancer (PAC) occurs in approximately 1 in 1000 pregnancies, and the incidence is expected to rise due to delayed childbearing (Silverstein et al. in JCO Oncol Pract 16:545-557, 2020; Woitek et al. in ESMO Open 1:e000017, 2016). Diagnosis and management of PACs are challenging and diagnosis is often delayed as symptoms may overlap with physiologic changes of pregnancy (Jha et al. in RadioGraphics 42:220005, 2022). These patients are best cared for by a multidisciplinary healthcare team composed of experts (Silverstein et al. in JCO Oncol Pract 16:545-557, 2020). Management of these patients must balance optimal maternal care with potentially harmful fetal effects. This involves honest, forthright, and sometimes difficult discussions between the care team and the patient throughout the entirety of care. Radiologists play a significant role in timely cancer diagnosis, staging and follow-up during and after pregnancy, accurate determination of gestational age, and in assessing fetal growth and well-being throughout pregnancy.

A Genomic Analysis of Esophageal Squamous Cell Carcinoma in Eastern Africa.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC. METHODS: We describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA). RESULTS: We observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort. CONCLUSIONS: This study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites. IMPACT: Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date.

Multidisciplinary Management of Cancer During Pregnancy.

Cancer during pregnancy is relatively rare but is increasing in frequency in countries in which the maternal child-bearing age continues to rise. The complexities of medical decision making are underscored by the need to weigh the potential benefits of any intervention for the mother against the risks to the fetus. A majority of diagnostic evaluations can be performed safely in the setting of pregnancy and should not be delayed. Noninvasive prenatal testing that shows discordance with fetal karyotype can be a clue to an underlying maternal malignancy. After diagnosis, a multidisciplinary team should formulate a care plan for both the mother and the fetus. Key topics for discussion should include the mother's prognosis, standard treatment plan, and predictions of how modifications for a continuing pregnancy will affect the treatment plan and overall prognosis. In the context of this knowledge, frank discussions about pregnancy termination should be addressed with the patient, if appropriate. Selection of a plan for oncologic management in the case of a pregnant woman is based on the type of cancer, the tumor biology, and the tumor stage. Additional complexities for pregnant patients are typically related to the gestational age of the fetus, the dynamic physiologic changes of pregnancy, and the limited safety data for administration of most anticancer therapies during pregnancy. In this article, we summarize data related to different classes of anticancer therapies as well as considerations for the management of selected cancers. Finally, we provide some key principles that should be considered in the management of patients with cancer during pregnancy.

Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period.

BACKGROUND: Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors. METHODS: We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer. RESULTS: All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERß), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified. DISCUSSION: CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

The Implications of the Supreme Court Decision to Overturn Roe v Wade for Women With Pregnancy-Associated Cancers.

This Viewpoint evaluates factors introduced by the overturn of Roe v Wade that will further complicate the complex, multidisciplinary decision-making involved in treating patients with pregnancy-associated cancer.