Pseudomyxoma Peritonei: A Challenging Clinical Diagnosis. Case Report and Review of the Literature.

Background: Pseudomyxoma peritonei (PMP) is a clinical entity of subtle onset abdominal pain, ascites, and distention associated with characteristic imaging. In most cases, laparoscopic exploration will give the definitive diagnosis and histopathologic verification. However, usually there are difficulties in the diagnosis of this disease. Case Report: Herein, we present a case of a 51-year-old female who developed ascites over 5 months. An investigational laparotomy established the diagnosis of PMP, after the discovery of a mucinous, grey-brown tumor that was CK20 positive and CK7 negative. Subsequently, chemotherapy with oxaliplatin combined with 5-FU (FOLFOX4 regimen), was initiated and the patient survived for 30 months. We also present a comprehensive review of the English literature concerning the different symptoms and radiological findings of this rare entity. According to the literature review, 35 cases of PMP with different clinical and radiological findings have been described. In the majority of the cases, ultrasound, computed tomography or magnetic resonance imaging was orientating towards a proper diagnosis before a diagnostic laparotomy. Conclusion: The combination of a clinical picture with the characteristic imaging findings enables a prompt diagnosis of PMP, making prognosis more favorable.

Caveolin-1 protein expression as a prognostic biomarker of gastrointestinal tumours: A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal (GI) cancers remain a major threat worldwide, accounting for over 30% of cancer deaths. The identification of novel prognostic biomarkers remains a challenge despite significant advances in the field. The CAV1 gene, encoding the caveolin-1 protein, remains enigmatic in cancer and carcinogenesis, as it has been proposed to act as both a tumour promoter and a tumour suppressor. METHODS: To analyse the differential role of caveolin-1 expression in both tumour cells and stroma in relation to prognosis in GI tumours, we performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; PROSPERO registration number: CRD42022299148. RESULTS: Our analysis showed that high levels of caveolin-1 in tumour cells were associated with poor prognosis and inferior overall survival (OS) in oesophageal and pancreatic cancer and hepatocellular carcinoma (HCC), but not in gastric and colorectal cancer. Importantly, our study showed that higher stromal caveolin-1 expression was associated with significantly longer OS and disease-free survival in colorectal cancer. Analysis of stromal caveolin-1 expression in the remaining tumours showed a similar trend, although it did not reach statistical significance. CONCLUSIONS: The data suggest that caveolin-1 expression in the tumour cells of oesophageal, pancreatic cancer and HCC and in the stroma of colorectal cancer may be an important novel predictive biomarker for the clinical management of these diseases in a curative setting. However, the main conclusion of our analysis is that caveolin-1 expression should always be assessed separately in stroma and tumour cells.

Metformin: A Promising Radiosensitizer in Neoadjuvant Rectal Cancer Treatment.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) decreases the risk of local recurrence after surgery in patients with locally advanced rectal cancer (LARC) and metformin is constantly gaining scientific interest due to its potentially radiosensitizing effect. OBJECTIVE: This review article aims to better clarify the role of metformin as a radiosensitizer in patients with LARC undergoing neoadjuvant concurrent chemoradiotherapy. METHODS: We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of metformin in the neoadjuvant setting of locally advanced rectal cancer. RESULTS: Our search resulted in 17 citations, of which 10 eventually fulfilled the inclusion criteria of our study. Promising results (improved tumor and nodal regression as well as higher pathologic complete response rate) have been occasionally documented with metformin use in some of the included studies. However, regarding survival and all-cause mortality, no significant difference has been found. CONCLUSION: Metformin might constitute a highly promising radiosensitizer in neoadjuvant LARC treatment attracting much scientific interest. Due to the lack of studies with high evidence, further advanced research is required to enhance the existing knowledge about its potential value in this field.

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.

COVID-19 Emotional and Mental Impact on Cancer Patients Receiving Radiotherapy: An Interpretation of Potential Explaining Descriptors.

Background: Significant changes in the accessibility and viability of health services have been observed during the COVID-19 period, particularly in vulnerable groups such as cancer patients. In this study, we described the impact of radical practice and perceived changes on cancer patients' mental well-being and investigated potential outcome descriptors. Methods: Generalized anxiety disorder assessment (GAD-7), patient health (PHQ-9), and World Health Organization-five well-being index (WHO-5) questionnaires were used to assess anxiety, depression, and mental well-being. Information on participants, disease baseline information, and COVID-19-related questions were collected, and related explanatory variables were included for statistical analysis. Results: The mean score values for anxiety, depression, and mental well-being were 4.7 ± 5.53, 4.9 ± 6.42, and 72.2 ± 18.53, respectively. GAD-7 and PHQ-9 scores were statistically associated (p < 0.001), while high values of GAD-7 and PHQ-9 questionnaires were related to low values of WHO-5 (p < 0.001).Using the GAD-7 scale, 16.2% of participants were classified as having mild anxiety (GAD-7 score: 5−9).Mild to more severe anxiety was significantly associated with a history of mental health conditions (p = 0.01, OR = 3.74, 95% CI [1.372−10.21]), and stage category (stage III/IV vs. I/II, p = 0.01, OR = 3.83, 95% CI [1.38−10.64]. From the participants, 36.2% were considered to have depression (PHQ-9 score ≥ 5). Depression was related with older patients (p = 0.05, OR = 1.63, 95% CI [1.16−2.3]), those with previous mental health conditions (p = 0.03, OR = 14.24, 95% CI [2.47−81.84]), those concerned about the COVID-19 impact on their cancer treatment (p = 0.027, OR = 0.19, 95% CI [0.045−0.82]) or those who felt that COVID-19 pandemic has affected mental health (p = 0.013, OR = 3.56, 95% CI [1.30−9.72]). Additionally, most participants (86.7%) had a good well-being score (WHO-5 score ≥ 50). Mental well-being seemed more reduced among stage I−III patients than stage IV patients (p = 0.014, OR = 0.12, 95% CI [0.023−0.65]). Conclusion: There is a necessity for comprehensive cancer care improvement. These patients' main concern related to cancer therapy, yet the group of patients who were mentally affected by the pandemic should be identified and supported.

Hyperthermic intraperitoneal chemotherapy for management of gastrointestinal and biliary tract malignancies: a systematic review and meta-analysis of randomized trials.

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) promised to transform the management of peritoneal carcinomatosis (PC). Forty years since the introduction of the technique, published data from randomized controlled trials (RCTs) remain scarce. We assessed the cumulative comprehensive available evidence on the use of HIPEC in gastrointestinal (GI) and biliary tract malignancies and established the current benchmark for GI HIPEC research in both the prevention and treatment of peritoneal metastases. Methods: RCTs were identified through a systematic search of Medline, Cochrane and Embase databases. Overall survival and progression-free survival were the outcomes of interest. Results: The search resulted in 13 RCTs for gastric cancer (10 on prophylactic and 3 on therapeutic HIPEC), 4 for colorectal cancer (2 on prophylactic and 2 on therapeutic HIPEC), and 1 for pancreatic cancer. No RCTs were identified that included other types of GI or biliary tract cancers. Current randomized evidence does not support any overall survival benefit from the use of HIPEC in the adjuvant setting for gastric cancer or for colorectal cancer in any setting. Despite the survival benefit noticed in the treatment of PC from gastric cancer (risk ratio 0.85, 95% confidence interval 0.77-0.93; P<0.001), the results were derived from only 190 patients. Conclusions: The current evidence from RCTs does not support the use of HIPEC in the treatment/prevention of PC in GI and biliary tract malignancies. HIPEC should continue to be considered experimental until level 1 evidence from properly designed international multicenter studies becomes available.

Markers of tumor inflammation as prognostic factors for overall survival in patients with advanced pancreatic cancer receiving first-line FOLFIRINOX chemotherapy.

BACKGROUND: Identifying pretreatment blood markers that distinguish prognostic groups of patients with advanced pancreatic ductal adenocarcinoma (PDAC) under first-line FOLFIRINOX chemotherapy has the potential to improve management of this condition. Aim of this study was to determine the prognostic utility of a range of pretreatment, inflammation-related, blood cell markers in this group of patients. MATERIAL AND METHODS: Data from a training cohort were analyzed to identify potential pretreatment blood markers correlating to survival outcomes. The most informative markers were further analyzed in a validation cohort comprised patients from a geographically separate cancer center undergoing the same treatment. RESULTS: A total of 138 consecutive patients receiving FOLFIRINOX chemotherapy between 2010 and 2019, constituted the training cohort. Neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte ratio (PLR) as well as the systemic inflammatory response index (SIRI) and CA19.9 showed prognostic significance in addition to tumor stage. A pretreatment SIRI score cutoff of 2.35 differentiated between a poor prognostic group with median overall survival (mOS) 5.1 months and a better prognostic group, mOS 12.5 months. SIRI ≤/> 2.35 was predictive of mOS in patients with locally advanced and metastatic PDAC. SIRI was confirmed as a prognostic marker in a validation cohort of 67 patients with mOS of 13.4 months and 6.3 months for those with SIRI ≤ 2.35 and >2.35, respectively. Additional analysis revealed baseline SIRI as being prognostic within additional subgroups of patients in both cohorts. CONCLUSIONS: This large, retrospective, analysis of real-world patients receiving first-line FOLFIRINOX chemotherapy for advanced PDAC has identified the pretreatment blood SIRI as a strong prognostic marker for survival. This will allow better counseling of patients with regards to the benefits of treatment, improved stratification within clinical trials, and potentially identify groups of patients for novel therapy trials as first-line treatment.

Next-Generation Sequencing of Circulating Tumor DNA Can Optimize Second-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer after Progression on anti-EGFR Therapy: Time to Rethink Our Approach.

BACKGROUND: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. SUMMARY: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions. KEY MESSAGES: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

Pancreaticobiliary Malignancies in the Emergency Room: Management of Acute Complications and Oncological Emergencies.

BACKGROUND: Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions. METHODS: Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented. RESULTS: The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented. CONCLUSION: Patients with PB malignancies are at increased risk of a wide variation of medical emergencies. Clinical knowledge, early recognition and collaboration with the relevant specialties are critical to manage these complications effectively, tailoring overall management around the actual prognosis and individuals' expectations.

Cutaneous soft tissue sarcomas: survival-related factors.

Cutaneous sarcomas are a heterogeneous group of rare mesenchymal neoplasms representing less than 1% of malignant tumors. Histology report remains the cornerstone for the diagnosis of these tumors. The most important clinicopathologic parameters related to prognosis include larger tumor size, high mitotic index, head and neck location, p53 mutations, depth of infiltration and histological grade, vascular and perineural invasion as well as the surgical margins status. Applying advanced biopsy techniques might offer more precise assessment of surgical margins, which constitutes a significant precondition for the management of these tumors. The management of cutaneous soft tissue sarcomas requires a multidisciplinary approach. Surgery remains the standard treatment, nonetheless adjuvant therapy may be required, consisting of radiotherapy, chemotherapy, and molecular targeted therapies to improve treatment outcomes. The role of molecular profiling in the treatment of uncontrolled disease is promising, but it may be offered to a relatively small proportion of patients and its use is still considered experimental in this setting. Due to the rarity of the disease, there is a need for knowledge and experience to be shared, pooled, organized and rationalized so that recent developments in medical science can have a major impact on the disease course. Multicenter clinical trials are needed to improve the care of patients with cutaneous sarcomas.

Prognostic significance and therapeutic implications of Caveolin-1 in gastrointestinal tract malignancies.

Caveolin-1 (CAV1) is expressed in several solid tumors both in cancerous cells as well as in tumor stroma and is reported to be related to cancer progression, metastasis, therapy resistance and clinical outcomes. Many studies report contrasting functions of this protein depending on the tumor cell model, the tumor type, or the stage of cancer studied. This protein is reported to function both as tumor suppressor and as tumor promoter. In this review, we aim to summarize translational and clinical studies that provide evidence of the role of CAV1 in tumor progression and survival outcome focusing on tumors of the gastrointestinal (GI) tract. Towards this aim, a detailed search has been performed for studies on the expression and the role of CAV1 in oesophageal, gastric, colorectal, pancreatic cancer and cholangiocarcinoma prognosis. We also review and discuss the implication of CAV1 in the outcome of pharmacological interventions. We conclude that CAV1 has the potential to become an important prognostic, and possibly predictive, biomarker in GI malignancies. It may also become a novel target towards the development of improved cancer therapies. However, it is obvious that there remains a lack of consensus on important issues such as the methodologies and cut-off levels in caveolin assessment. This ultimately result in many studies being contradictory not only in terms of the role of CAV1 as a tumor-promoting or suppressing gene but also in terms of the tumor compartment in which the levels of this protein may be of clinical significance. Addressing these important technical issues, in conjunction with a further elucidation of the role of CAV1 in tumor formation and progression, will delineate the importance of CAV1 in prognostic and therapeutic perspectives.

Modification to Systemic Anticancer Therapy at the Start of the COVID-19 Pandemic and its Overall Impact on Survival Outcomes in Patients with Colorectal Cancer.

BACKGROUND: Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians' decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer. PATIENTS AND METHODS: Electronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians' decision were assessed. RESULTS: A total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48). CONCLUSION: During the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

YAP/Hippo Pathway and Cancer Immunity: It Takes Two to Tango.

Hippo pathway with its main molecule YAP is a crucial pathway for development, tissue homeostasis, wound healing, tissue regeneration, and cancer. In this review, we discuss the multiple effects of the YAP/Hippo pathway in the immune system and cancer. We analyzed a series of effects: extracellular vesicles enhanced immunity through inhibition of LATS1/2, ways of modulation of the tumor microenvironment, YAP- and TAZ-mediated upregulation of PDL1, high expression of YAP and PDL1 in EGFR-TKI-resistant cells, enhanced YAP activity in inflammation, and the effect of the Hippo pathway on T cells, B cells, Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs). These pleiotropic effects render the YAP and Hippo pathway a key pathway for exploitation in the future, in order to enhance our immunotherapy treatment strategies in oncology.

Immunotherapy Efficacy in the Initial Lines of Treatment in Advanced Upper Gastrointestinal Malignancies: A Systematic Review of the Literature.

Background: The therapeutic role of immune checkpoint inhibitors (ICIs) has represented the cutting edge of clinical research in upper gastrointestinal (GI) malignancies, with these agents now included in the armamentarium of treatment options for advanced gastric and esophageal cancers. Methods: We performed a systematic literature review and pooled analysis to map out the currently available robust clinical evidence for the use of ICIs in upper GI cancers. Immunotherapy (IO), either as monotherapy or in combination with chemotherapy, and its role in first-line, maintenance, and second-line settings, as well as in specific clinical and biological subgroups, were critically appraised. All statistical tests were 2-sided. Results: ICIs, in combination with chemotherapy, have provided statistically significant overall survival benefit in the first-line setting in gastric and gastro-esophageal adenocarcinomas (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.76 to 0.90, P < .001; based on 4 studies) and esophageal squamous cell carcinoma (HR = 0.72, 95% CI = 0.64 to 0.81, P < .001; based on 3 studies), albeit with heterogeneous efficacy according to biomarker expression. Patients with esophageal squamous cell carcinoma, and in particular high programmed cell death ligand-1 expression, derive survival benefit when treated with IO in the second-line setting (HR = 0.74, 95% CI = 0.68 to 0.82, P < .001; for any level of programmed cell death ligand-1 expression). Clinical trials interrogating the combination of IO with chemotherapy in second-line treatment should be seriously considered in upper GI adenocarcinomas. The role of maintenance IO after initial disease control is still unclear and cannot be recommended. Impressive response rates and survival benefit from IO have been reported in patients with microsatellite instability-high tumors (HR = 0.33, 95% CI = 0.19 to 0.57, P < .001), and this warrants further prospective biomarker-driven studies. Conclusions: IO is changing the treatment landscape in upper GI malignancies. The rapidly developing evidence in the field needs to be critically appraised while further validation of the existing information from ongoing trials is awaited.

The COVID-19 survey pandemic: a critical approach.

COVID-19 pandemic has obviously affected patients' behavior towards seeking medical help as well as physicians' decision in the management of emergencies. Our recent experience as surgeons at a COVID-19 referral hospital revealed cases which share an alerting characteristic: the delay in appropriate management. Unfortunately for COVID-19 negative patients a "coronacentric" health system has been adopted. In view of measures applied to avoid spread of the disease, a significant delay in patients' presentation as well as in their in-hospital management is observed. We present cases where delay in appropriate management affected the patients' outcome and underline the fact that balancing between COVID-19 safety measures and a patient who needs urgent treatment can be very challenging and stressful.

Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer: The GO2 Phase 3 Randomized Clinical Trial.

Importance: Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. Objective: The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Design, Setting, and Participants: This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty. Interventions: There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. Main Outcomes and Measures: First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results: A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance: This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registration: isrctn.org Identifier: ISRCTN44687907.

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.

Interior Design: A New Perspective in Supportive Care of Patients with Acute Onset of Debilitating Diseases.

Background: Upon the onset of a debilitating rapidly evolving condition (such as cancer or a rapidly progressing myopathy, neuropathy, respiratory disease, or a severe traumatic injury), individuals have limited time to find a new home or make radical structural modifications in their residence. How the affected patients can continue sharing the same house with their families, while meeting their own special requirements, is thus rising as a critical issue. Household and daily routine rearrangements, either temporary or permanent, may be necessary, to ameliorate the life of patients with impairments, lasting for months or even years. Objectives: Interior design may provide a highly efficient "living" palliation for debilitating medical conditions directly at patients' home-site. Methods: Research of relevant literature, using keywords "debilitating conditions," "home care," "end of life care," "care of advanced cancer patients," "care of patients with mental disorders," "home care of covid-19 affected patients," and "care of patients with degenerative illnesses." Results: We found that patients and their relatives may not be aware of the probable interior design solutions to their daily life challenges, imposed by a disease-related impairment. In parallel, interior design experts may equally be unaware of these issues, as well as of who needs the available solutions.Similarly, medical and architectural sciences are not connected, eventually failing to meet patients' everyday needs. Conclusions: Interior architecture and health scientists are called to cooperate, aiming to provide a highly efficient and meaningful support to patients and families affected by unforeseen debilitating medical conditions.

Synthesis of Recommendations From 25 Countries and 31 Oncology Societies: How to Navigate Through Covid-19 Labyrinth.

INTRODUCTION: Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak. METHODS: We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies. RESULTS: By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis. CONCLUSIONS: In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally.