Epidemiologic data indicate a significant increase in the incidence of colorectal cancer in younger populations in the past three decades. Moreover, recent evidence also demonstrates a similar trend in gastric, pancreatic, and biliary tract cancers. A majority of these early-onset cases are sporadic and lack hereditary or familial background, implying a potential key role for behavioral, lifestyle, nutritional, microbial, and environmental factors. This review explores the current data on early-onset gastrointestinal cancer, exploring the etiology, unique treatment considerations for this population, future challenges, as well as implications for research and practice. Significance: The worrisome trend of an increasing incidence of early-onset gastrointestinal cancers appears to be correlated with nonhereditary etiologies in which behavioral, lifestyle, nutritional, microbial, and environmental factors, as well as host mechanisms, may play a key role. Further epidemiologic and pathogenetic research is urgently needed to better understand the underlying mechanisms and to develop preventive strategies and tailored early detection. Young patients with gastrointestinal cancer face unique challenges and unmet needs. These must be addressed in the future management of the disease to minimize treatment-related somatic morbidity and prevent psychosocial sequelae.

Background: Young cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce ovarian toxicity via an impact on the entire ovary. The role of doxorubicin in potential ovarian failure remains obscure. Our intention was to elucidate doxorubicin-related toxicity within ovaries. Methods: Female mice were injected intraperitoneally with 7.5 or 10 mg/kg doxorubicin and their ovaries were visualized in vivo by high resolution MRI, one day and one month following treatment. Ovaries of other treated mice were excised and weighed at the same post-treatment intervals. Ovarian histological sections were stained for TUNEL or active caspase-3 and follicles were counted and categorized. Ovulation rates were evaluated in superovulated female mice treated with doxorubicin. Results: A single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post treatment. A dramatic reduction in ovulation rate was observed one week after treatment, followed by a partial recovery at one month. Histological examination revealed positive staining of TUNEL and active caspase-3. We observed a significant reduction in the population of secondary and primordial follicles one month following treatment. Conclusions: Our results may imply a mechanism of chemotherapy-induced ovarian toxicity, manifested by reduced ovulation and accompanied by a reduction in ovarian size, caused probably by an acute insult to the ovary.

The COVID-19 pandemic has been associated with inferior clinical outcomes in patients with cancer owing to altered delivery of care and potential high-risk for SARS-CoV-2 infection in distinct subpopulations. Studies have indicated that patients with cancer may experience a severe COVID-19 clinical course, with metastatic cancer, hematologic malignant neoplasms, and lung cancer recognized as leading risk factors.^1,2 Nevertheless, other studies reported that patients with cancer did not appear to have additional risk compared with the general population and, moreover, that COVID-19 severity was associated with patient age and cardiovascular comorbidities, which are prominent general risk factors in patients with COVID-19.³ The association between the pandemic and care delivery appears less controversial. Routine clinical care has been disrupted throughout an extended period while health care clinicians and professional organizations continuously modified recommendations based on risk-benefit assessment.⁴ Owing to the need to alleviate the magnitude of the pandemic and move toward a return to normalcy, effective prophylactic vaccines have been developed and studied in an expedited process.

Purpose Dyspnea is one of the most distressing symptoms experienced by terminally ill cancer patients. This study aimed to evaluate the role of interventions for the palliation of dyspnea. Methods We conducted a systematic review of randomized controlled trials assessing all pharmacologic and nonpharmacologic interventions for dyspnea palliation in cancer patients, and searched the Cochrane Library, MEDLINE, conference proceedings, and references. Two reviewers independently appraised the quality of trials and extracted data. Results Our search yielded 18 trials. Fourteen evaluated pharmacologic interventions: seven assessing opioids (a total of 256 patients), five assessing oxygen (137 patients), one assessing helium-enriched air, and one assessing furosemide. Four trials evaluated nonpharmacologic interventions (403 patients). The administration of subcutaneous morphine resulted in a significant reduction in dyspnea Visual Analog Scale (VAS) compared with placebo. No difference was observed in dyspnea VAS score when nebulized morphine was compared with subcutaneous morphine, although patients preferred the nebulized route. The addition of benzodiazepines to morphine was significantly more effective than morphine alone, without additional adverse effects. Oxygen was not superior to air for alleviating dyspnea, except for patients with hypoxemia. Nursing-led interventions improved breathlessness. Acupuncture was not beneficial. Conclusion Our review supports the use of opioids for dyspnea relief in cancer patients. The use of supplemental oxygen to alleviate dyspnea can be recommended only in patients with hypoxemia. Nursing-led nonpharmacologic interventions seem valuable. Only a few studies addressing this question were performed. Thus, further studies evaluating interventions for alleviating dyspnea are warranted.

PURPOSE: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non–cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.

Gastric cancer is the third most lethal cancer worldwide, and evaluation of the genomic status of gastric cancer cells has not translated into effective prognostic or therapeutic strategies. We therefore hypothesize that outcomes may depend on the tumor microenvironment (TME), in particular, cancer-associated fibroblasts (CAF). However, very little is known about the role of CAFs in gastric cancer. To address this, we mapped the transcriptional landscape of human gastric cancer stroma by microdissection and RNA sequencing of CAFs from patients with gastric cancer. A stromal gene signature was associated with poor disease outcome, and the transcription factor heat shock factor 1 (HSF1) regulated the signature. HSF1 upregulated inhibin subunit beta A and thrombospondin 2, which were secreted in CAF-derived extracellular vesicles to the TME to promote cancer. Together, our work provides the first transcriptional map of human gastric cancer stroma and highlights HSF1 and its transcriptional targets as potential diagnostic and therapeutic targets in the genomically stable tumor microenvironment. Significance: This study shows how HSF1 regulates a stromal transcriptional program associated with aggressive gastric cancer and identifies multiple proteins within this program as candidates for therapeutic intervention.