The Mental Health Burden of Patients with Colorectal Cancer Receiving Care during the COVID-19 Pandemic: Results of the PICO-SM Study.

The COVID-19 pandemic has resulted in unprecedented changes to the lives of patients with cancer. To evaluate the impact of the COVID-19 pandemic on the mental health and well-being of patients with colorectal cancer, we conducted a prospective longitudinal questionnaire study at a UK tertiary cancer centre. In total, 216 participants were included: mean age 65 years, 57% (n = 122) male, 92% (n = 198) of white ethnicity. Amongst participants who completed the screening psychometric questionnaire, 24% (n = 48/203) reported anxiety (GAD-7 ≥ 5), 15% (n = 31/204) depressive symptoms (PHQ-9 ≥ 10), 3% (n = 5/190) probable post-traumatic stress disorder (PC-PTSD-5 ≥ 4), and 31% (n = 66/213) poor well-being (WHO-5 < 50). In the subgroup (n = 95/216, 44%) who consented to and completed a follow-up survey 6 months later, there was a significant increase in the number of participants at risk of depression (4% vs. 13%, p = 0.021). Self-reported concern about the COVID-19 pandemic impacting one's mental health is associated with increased likelihood of anxiety, depression, and poor well-being, in respective multivariate analyses. In conclusion, screening for the mental health impact of the COVID-19 pandemic is essential to ensure timely action from all key stakeholders and to avoid potentially longer-term detrimental consequences.

The Impact of Changes in Service Delivery in Patients With Colorectal Cancer During the Initial Phase of the COVID-19 Pandemic.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has imposed significant changes in cancer service delivery resulting in increased anxiety and distress in both patients and clinicians. We aimed to investigate how these changes have been perceived by patients diagnosed with colorectal cancer and identify determinants of increased anxiety. PATIENTS AND METHODS: An anonymized 32-item survey in the specialized lower gastrointestinal cancer outpatient clinics at a tertiary cancer center in North West England between May 18 and July 1, 2020. Self-reported anxiety was based on the General Anxiety Disorder-7 screening tool. RESULTS: Of 143 participants who completed the survey (response rate, 67%), 115 (82%) were male, and the median age group was 61 to 70 years. A total of 112 (78%) participants had telephone consultation (83% met needs), and 57 (40%) had radiologic scan results discussed over the phone (96% met needs). In total, 23 (18%) participants were considered to have anxiety (General Anxiety Disorder-7 score ≥ 5), with 7 (5.5%) scoring for moderate or severe anxiety. Those concerned about getting COVID-19 infection, and worried COVID-19 would have effect on their mental health, and affect their experience of cancer care, were most likely to have anxiety (P < .05, multivariate analysis). The majority did not feel they needed support during this phase of the pandemic. Participants felt that friends and family had been very supportive, but less so the primary care services (P < .05). CONCLUSIONS: The findings of this survey suggest that some of the service changes implemented may have already improved the overall experience of cancer care among patients with colorectal cancer at our institute. Reassuringly, the incidence of participants with moderate to severe anxiety levels during the peak of COVID-19 in the United Kingdom was much lower than anticipated. Importantly, patients were much more concerned about their cancer treatment than COVID-19, emphasizing the need to continue to provide comprehensive cancer care even with a "second wave" of COVID-19.

The Influence of Adjuvant Systemic Regimens on Contralateral Breast Cancer Risk and Receptor Subtype.

BACKGROUND: An increasing number of breast cancer (BC) survivors are at risk of developing contralateral breast cancer (CBC). We aimed to investigate the influence of various adjuvant systemic regimens on, subtype-specific, risk of CBC. METHODS: This population-based cohort study included female patients diagnosed with first invasive BC between 2003 and 2010; follow-up was complete until 2016. Clinico-pathological data were obtained from the Netherlands Cancer Registry and additional data on receptor status through linkage with PALGA: the Dutch Pathology Registry. Cumulative incidences (death and distant metastases as competing risk) and hazard ratios (HRs) were estimated for all invasive metachronous CBC and CBC subtypes. RESULTS: Of 83 144 BC patients, 2816 developed a CBC; the 10-year cumulative incidence was 3.8% (95% confidence interval [CI] = 3.7% to 4.0%). Overall, adjuvant chemotherapy (HR = 0.70, 95% CI = 0.62 to 0.80), endocrine therapy (HR = 0.46, 95% CI = 0.41 to 0.52), and trastuzumab with chemotherapy (HR = 0.57, 95% CI = 0.45 to 0.73) were strongly associated with a reduced CBC risk. Specifically, taxane-containing chemotherapy (HR = 0.48, 95% CI = 0.36 to 0.62) and aromatase inhibitors (HR = 0.32, 95% CI = 0.23 to 0.44) were associated with a large CBC risk reduction. More detailed analyses showed that endocrine therapy statistically significantly decreased the risk of estrogen receptor (ER)-positive CBC (HR = 0.41, 95% CI = 0.36 to 0.47) but not ER-negative CBC (HR = 1.32, 95% CI = 0.90 to 1.93) compared with no endocrine therapy. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5 years of follow-up (HR = 2.84, 95% CI = 1.62 to 4.99) compared with patients not receiving chemotherapy for ER-negative first BC. CONCLUSION: Endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy reduce CBC risk. However, each adjuvant therapy regimen had a different impact on the CBC subtype distribution. Taxane-containing chemotherapy and aromatase inhibitors were associated with the largest CBC risk reduction.

Risk factors for metachronous contralateral breast cancer: A systematic review and meta-analysis.

BACKGROUND: The risk of developing metachronous contralateral breast cancer (CBC) is a recurrent topic at the outpatient clinic. We aimed to provide CBC risk estimates of published patient, pathological, and primary breast cancer (PBC) treatment-related factors. METHODS: PubMed was searched for publications on factors associated with CBC risk. Meta-analyses were performed with grouping of studies by mutation status (i.e., BRCA1, BRCA2, CHEK2 c.1100delC), familial cohorts, and general population-based cohorts. RESULTS: Sixty-eight papers satisfied our inclusion criteria. Strong associations with CBC were found for carrying a BRCA1 (RR = 3.7; 95%CI:2.8-4.9), BRCA2 (RR = 2.8; 95%CI:1.8-4.3) or CHEK2 c.1100delC (RR = 2.7; 95%CI:2.0-3.7) mutation. In population-based cohorts, PBC family history (RR = 1.8; 95%CI:1.2-2.6), body mass index (BMI) ≥30 kg/m2 (RR = 1.5; 95%CI:1.3-1.9), lobular PBC (RR = 1.4; 95%CI:1.1-1.8), estrogen receptor-negative PBC (RR = 1.5; 95%CI:1.0-2.3) and treatment with radiotherapy <40 years (RR = 1.4; 95%CI:1.1-1.7) was associated with increased CBC risk. Older age at PBC diagnosis (RR per decade = 0.93; 95%CI:0.88-0.98), and treatment with chemotherapy (RR = 0.7; 95%CI:0.6-0.8) or endocrine therapy (RR = 0.6; 95%CI:0.5-0.7) were associated with decreased CBC risk. CONCLUSIONS: Mutation status, family history, and PBC treatment are key factors for CBC risk. Age at PBC diagnosis, BMI, lobular histology and hormone receptor status have weaker associations and should be considered in combination with key factors to accurately predict CBC risk.

Independent replication of polymorphisms predicting toxicity in breast cancer patients randomized between dose-dense and docetaxel-containing adjuvant chemotherapy.

INTRODUCTION: Although pharmacogenomics has evolved substantially, a predictive test for chemotherapy toxicity is still lacking. We compared the toxicity of adjuvant dose-dense doxorubicin-cyclophosphamide (ddAC) and docetaxel-doxorubicin-cyclophosphamide (TAC) in a randomized multicenter phase III trial and replicated previously reported associations between genotypes and toxicity. RESULTS: 646 patients (97%) were evaluable for toxicity (grade 2 and higher). Whereas AN was more frequent after ddAC (P < 0.001), TAC treated patients more often had PNP (P < 0.001). We could replicate 2 previously reported associations: TECTA (rs1829; OR 4.18, 95% CI 1.84-9.51, P = 0.001) with PNP, and GSTP1 (rs1138272; OR 2.04, 95% CI 1.13-3.68, P = 0.018) with PNP. MATERIALS AND METHODS: Patients with pT1-3, pN0-3 breast cancer were randomized between six cycles A60C600 every 2 weeks or T75A50C500 every 3 weeks. Associations of 13 previously reported single nucleotide polymorphisms (SNPs) with the most frequent toxicities: anemia (AN), febrile neutropenia (FN) and peripheral neuropathy (PNP) were analyzed using logistic regression models. CONCLUSIONS: In this independent replication, we could replicate an association between 2 out of 13 SNPs and chemotherapy toxicities. These results warrant further validation in order to enable tailored treatment for breast cancer patients.

Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age.

The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2 (BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3­34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45­1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60­3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy.