Clinical colorectal cancer最新文献

Background

Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression.

Materials and Methods

The impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing.

Results

High ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB.

Conclusion

ITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.

The number of colon cancer survivors in the United States is increasing due to improved early detection, better treatments that extend survival, and the growing aging population who are at high risk for cancer. Following initial active treatment, colon cancer survivors experience a wide range of long-term physical, psychological, and socio-economic effects that impact their overall well-being. Healthcare providers caring for survivors need to prioritize not only monitoring for cancer recurrence but also optimizing their overall health through addressing these long-term effects; managing their comorbidities; promoting healthy behaviors (like exercise, nutrition, and weight loss); and screening for a second primary cancer depending on their risk. Personalized survivorship care plans should be formulated clearly outlining the roles of various healthcare providers involved in their care. Our review article focuses on these various aspects of colon cancer survivorship, including surveillance for cancer recurrence specific to those who received adjuvant chemotherapy with curative intent.

Patients cope in different ways when living with an incurable cancer. These varied coping styles impact how oncology providers communicate with patients. If providers do not tailor communication with a general understanding of how a patient is coping, this risks miscommunication with the patient, inaccurate disease understanding, and suboptimal care. This review explores the spectrum of coping patterns that influence a patient's behaviors and communication with their oncology team throughout a cancer course. We then review several strategies to assist with coping in order to provide more transparent communication throughout the cancer course. Patients express coping styles on a spectrum, from “avoidant” to “resistant” to “engaged.” The “avoidant” and “resistant” coping styles often impede transparent communication between patient and provider due to expressions of unrealistic hope by the patient. Several communication skills can improve patient coping and readiness to discuss prognostic information about the cancer, which will better facilitate conversations around end of life and readiness to stop cancer treatment and initiate hospice when indicated. Understanding the spectrum of coping styles and stress responses by patients and families can improve shared understanding between patient and provider as well as a sense of partnership with patients and families.

Introduction

Pseudomyxoma peritonei (PMP) is a rare, slow growing tumor, traditionally considered chemoresistant. The only curative approach is cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). At disease relapse, or in patients with inoperable disease at diagnosis, no standard treatment has been defined, though nonrandomized series showed promising results with fluoropyrimidine-based regimens.

Patients and Methods

We conducted a prospective study in patients with relapsed or unresectable PMP and confirmed disease progression at baseline. Patients received MMC (7 mg/m² every 6 weeks, up to a maximum of 4 cycles) plus metronomic capecitabine (625 mg/sqm/day b.i.d.) and bevacizumab (7.5 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), overall response rate according to RECIST v1.1 criteria, serum markers response and safety.

Results

Fifteen patients were included. At a median follow-up of 26.1 months (IQR, 17.7-49.6), median PFS was 17.9 months (95% CI, 11.0-NE), with 1-year PFS and OS rates of 73% and 87%. Safety profile was manageable, with only 13% G3/G4 treatment-related adverse events.

Conclusion

Metronomic capecitabine, bevacizumab, and MMC are an active regimen in advanced and progressive PMP and favorably compares with historical series.

Older adults share a growing burden of cancer morbidity and mortality. This is present across the spectrum of oncologic diagnoses and is particularly true with colorectal cancer (CRC), where older adults continue to share the burden of diagnoses. However, optimal cancer treatment decision making in older adults remains a significant challenge, as the majority of previous clinical trials shaping the current treatment landscape have focused on younger patients, often with more robust performance status and fewer medical comorbid conditions. The heterogeneous aging process of older adults with CRC necessitates a personalized treatment approach, as approximately three-quarters of older adults with CRC also have a concominant geriatric syndrome and more than half of older adults with CRC are pre-frail or frail. Treatment decisions shoud be multifaceted, including consultation with the patient and their familes regarding their wishes, with consideration of the patient's quality of life, functional status, medical comorbid conditions, social support, and treatment toxicity risk. Geriatric assessment is a systematic and validated approach to assess an older adults's potential strengths and vulnerabilities, which can in turn be used to assist with comprehensive cancer care planning and support. In this review, we will summarize current treatment approaches for older adults with CRC, with a particular focus on the incorporation of the geriatric assessment.

Background

It remains unclear whether radiation therapy (RT) has an impact on the development of secondary primary cancer (SC) in rectal cancer (RC) patients, especially within the true pelvis.

Aim

To examine the incidence of SC in a population-based cohort of RC after surgical treatment with or without radiation therapy (RT, NRT).

Patients and Methods

The epidemiological cohort consisting of 13,919 RC patients with primary M0 stage diagnosed between 1998 and 2019 was collected from cancer registry data of Upper Bavaria. Competing risk analyses were conducted regarding the development of SC on 11 687 first malignancies, stratified by RT/NRT. A propensity score (PS) was generated by logistic regression modeling of RT to repeat competing risk analyses on a PS-matched cohort.

Results

The median age (interquartile range) of the epidemiological cohort was 68.9 years (60.4-76.7). About 60.8%, were men, 38.7% had UICC III, 35.8% of tumors were localized lower than 8 cm, 41.3% underwent RT. Only 17.1% of patients older than 80 years at diagnosis received RT. In general, RT patients were 5 years younger than NRT patients (65.9 years [58.0-73.0] vs. 71.3 years [62.4-79.2], P < .0001). The 20-year cumulative incidence of SC was 16.5% in RT and 17.4% in NRT patients (P = .2298). Men with RT had a lower risk of prostate cancer (HR = 0.55, 95%CI [0.34-0.91], P = .0168). In the PS-matched cohort, RT patients had a significantly higher risk of bladder cancer during follow-up (10-year cumulative incidence of 1.1% vs. 0.6% in NRT). The direction of the RT effects in men and women and different tumor sites may cancel each other.

Conclusion

A protective effect of RT in rectal cancer patients on developing prostate SC by half is reproduced. Further analyses studying the long-term SC risks of RT should essentially focus on stratification by sex, and focus on more recent data.

Introduction

Microsatellite stable metastatic colorectal cancer (MSS mCRC) is largely refractory to immune checkpoint inhibition. We hypothesized that a combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade would induce a local focus of immune stimulation, evoking a systemic immune response.

Patients and Methods

In this phase I single-institution study, patients with MSS mCRC were treated with a priming dose of s.c vidutolimod, 3 intratumoral injections of vidutolimod and radiosurgery, combined with nivolumab and ipilimumab. Cytokine levels were measured at baseline and at 7 (± 2) weeks. Patients were accrued to 4 consecutive cohorts: (1) Safety run-in without radiosurgery, (2) Radiosurgery prior to intratumoral therapy, (3) Radiosurgery prior to intratumoral therapy with a condensed timeline, and (4) Radiosurgery to extrahepatic lesion following completion of intratumoral therapy.

Results

A total of 19 patients were accrued. Median age was 59 years (range 40-71), 68% were male, median number of previous systemic treatments was 3 (range 2-5). None of the patients responded, aside from 1 patient, attributed to high tumor mutational burden. Grade 3 liver toxicity was reported in 0%, 0%, 75%, and 17% in cohorts 1 to 4, respectively. Systemic levels of CXCL10 and IL-10 increased, with a median of 407 versus 78 pg/mL (P = .01), and 66 versus 40 pg/mL (P = .03), respectively.

Conclusions

The combination of intratumoral vidutolimod, radiosurgery, nivolumab and ipilimumab was not found to be efficacious in MSS mCRC with liver metastases. The juxtaposition of liver irradiation and intratumoral vidutolimod injection was associated with high hepatic toxicity.

Background

Colorectal cancer (CRC) preferentially affects older adults. Modifiable factors, such as anxiety, can be measured as part of cancer-specific geriatric assessments (GA) completed prior to the start of treatment. We hypothesized that anxiety is prevalent among older adults with CRC and is associated with increased depression, increased frailty, and impaired health-related quality of life (HRQOL).

Patients and Methods

Patients ≥60 years old with newly diagnosed CRC completed a cancer-specific GA called the Cancer and Aging Resilience Evaluation (CARE). Between September 2017 and February 2023, we analyzed patients with CRC who had not yet received any systemic treatment. Anxiety was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4-item short form and reported as t-scores. We used modified Poisson models with robust variance estimation to assess for differences in the prevalence of depression, frailty, and impaired HRQOL.

Results

We analyzed 277 older adults with CRC. The median age of the study sample was 68 years. 57% were male, 72% were non-Hispanic White, and most had advanced CRC (35% stage III and 39% stage IV). Moderate/severe anxiety was present in 17% of older adults with newly diagnosed CRC. In adjusted models, as compared to patients without moderate/severe anxiety, patients with moderate/severe anxiety had significantly increased risk of depression (prevalence ratio [PR] 7.60, CI 4.90-11.78), frailty (PR 4.93, CI 3.01-8.07), impaired physical HRQOL (PR 3.57, CI 2.03-6.28), and impaired mental HRQOL (PR 3.82, CI 2.12-6.89).

Conclusion

Among older adults with CRC, anxiety is associated with increased depression and frailty as well as reduced HRQOL.

Background

Neoadjuvant chemoradiotherapy (nCRT) is the standard of care in locally advanced rectal cancer (LARC). However, radiation therapy is thought to increase operative difficulty due to induction of fibrosis. Total neoadjuvant therapy (TNT) protocols increase the time between completion of radiation and surgical resection which may lead to increased operative difficulty and complications.

Methods

A single institution retrospective review of patients ≥18 years with LARC undergoing nCRT from 2015 to 2022. Patients were dichotomized in 2 cohorts: <90 days from radiation to surgery (recent radiation), and ≥90 days from radiation to surgery (distant radiation). Institutional data was compared to National Surgical Quality Improvement Program (NSQIP) rectal cancer data from 2016 to 2020. Outcomes included intraoperative complications, 30-day morbidity, and oncologic outcomes.

Results

One hundred forty-six institutional patients included, 120 had recent radiation, 26 had distant radiation. Thirty-day morbidity and intraoperative complications did not differ. There was greater radial margin positivity (7% vs. 24%), fewer lymph nodes harvested (17 ± 5 vs. 15 ± 6), and a lower rate of complete mesorectal dissection (88% vs. 65%,) in distant radiation patients 3059 patients were included in NSQIP analysis, 2029 completed radiation <90 days before surgery and 1030 without radiation 90 days before surgery. Patients without radiation 90 days preoperatively had more radial margin positivity (9.2% vs. 4.6%), organ space infection (8.6% vs. 6.4%), and pneumonia (2.2% vs. 0.9%).

Conclusion

The present study suggests that increased time between radiation and surgery results in more challenging dissection with less complete mesorectal dissection and increased radial margin positivity without increasing technical complications.