Prognostic Factor In Cancer Patients Research Articles

Elevated serum magnesium levels prompt favourable outcomes in cancer patients treated with immune checkpoint blockers

BackgroundMagnesium deficiency influences the activation and cytotoxicity of immune cells. Nevertheless, whether serum magnesium levels influence the clinical outcomes of immune checkpoint blockers (ICBs) treatment still remains ambiguous. There is an urgent need for clinical research to elucidate the relationship between serum magnesium levels and the outcomes of ICB therapy. Such insights could offer new perspectives on immunotherapy for cancer. MethodsA multi-center retrospective study involving in pan-cancer patients treated with ICBs at three large cancer centers from August 2012 to May 2023 was conducted. The primary objective was to assess the correlation between serum magnesium levels and therapeutic response in patients receiving ICBs, and further evaluate the associations between serum magnesium levels and progression-free survival (PFS) and overall survival (OS). ResultsA total of 1441 patients treated with ICBs, including 1042 with lung cancer, 270 with esophageal cancer, and 129 with Hodgkin lymphoma, were enrolled in this study. We found that patients with elevated serum magnesium levels exhibited a favourable response to ICBs treatment. The optimal cut-off point for serum magnesium level (0.79 mmol/L) was applied for stratifying patients into distinct groups. In the three tumor cohorts, patients in high magnesium level group (Mg2+ ≥ 0.79 mmol/L) had longer PFS and OS than those in low magnesium level group (Mg2+ < 0.79 mmol/L). Univariate and multivariate analyses confirmed that the serum Mg2+ level serves as an independent prognostic factor for cancer patients receiving ICBs therapy. ConclusionOur multi-center study demonstrated that among patients receiving ICBs therapy, those with elevated serum magnesium levels exhibit significantly better clinical outcomes than those with low serum magnesium levels. Further prospective validation studies are needed to confirm these findings.

Prevalence and risks of intravenous chemotherapy-induced severe neutropenia in solid cancers: a multicenter retrospective cohort study on real-life data.

We aimed at identifying prevalence, clinical outcomes and prognostic factors in cancer patients with intravenous chemotherapy-induced severe neutropenia (ICISN). In this multicenter retrospective cohort study on the clinical data warehouse of Greater Paris University Hospitals (AP-HP), we included all adult patients with solid cancer hospitalized between 2016 and 2021 with intravenous chemotherapy within 30 days prior to severe neutropenia (D70 or D611 ICD-10 codes AND a neutrophil count < 500/mm3). The primary endpoint was referral to intensive care unit (ICU) or death within 30 days. We collected cancer, patient, and treatment characteristics. Among 141,586 cancer inpatients, 40,660 received chemotherapy among whom 661 (1.6%) had ICISN. Median age was 63 years (interquartile range (IQR), 54-70) and 330 patients (49%) were female. The median Charlson score was 10 (IQR, 8-11). Main primary cancers were lung (n = 204, 31%) and breast (n = 87, 13%). Advanced cancers were found in 551 patients (83%), 331 (50%) were in 1st line of chemotherapy, 284 (42%) in the 1st cycle of the current line and 149 (22%) had primary G-CSF. Documented bacterial (mostly gram-negative bacilli) and fungal infections were observed in 113 (17%) and 19 (3%) patients; 58 (9%) were transferred to ICU and 82 (12%) died within 30 days, 372 (56%) patients received subsequent chemotherapy. Independent prognostic factors were the level of monocyte, lymphocyte counts or albuminemia and a documented bacterial infection, while Charlson index and primary prophylactic G-CSF were not associated with patient clinical outcomes. Despite the use of primary G-CSF, ICISN remains a frequent event, which leads to ICU death in one on five cases Some prognostic factors of severity have been highlighted and could help clinicians to prevent severe complications.

Oncolytic herpes simplex virus propagates tertiary lymphoid structure formation via CXCL10/CXCR3 to boost antitumor immunity.

Inducing tertiary lymphoid structure (TLS) formation can fuel antitumor immunity. It is necessary to create mouse models containing TLS to explore strategies of TLS formation. Oncolytic herpes simplex virus-1 (oHSV) exhibited intense effects in preclinical and clinical trials. However, the role of oHSV in TLS formation remains to be elucidated. Here, we observed the presence of TLS in 4MOSC1 and MC38 subcutaneous tumour models. Interestingly, oHSV evoked TLS formation, and increased infiltration of B cells and stem-like TCF1+CD8+ T cells proliferation. Mechanistically, oHSV increased the expression of TLS-related chemokines, along with upregulated CXCL10/CXCR3 to facilitate TLS formation. Notably, CXCL10 and CXCR3 were favourable prognostic factors for cancer patients, and closely related with immune cells infiltration. Inhibiting CXCL10/CXCR3 reduced TCF1+CD8+ T cells and granzyme B expression, and impaired oHSV-mediated TLS formation. Furthermore, oHSV-mediated TLS formation revealed superior response and survival rate when combined with αPD-1 treatment. Collectively, these findings indicate that oHSV recruits stem-like TCF1+CD8+ T cells through CXCL10/CXCR3 pathway to propagate TLS formation, and warrants future antitumor immunity development.

Death associated protein kinase 1 predicts the prognosis and the immunotherapy response of various cancers.

Death Associated Protein Kinase 1 (DAPK1) is a calcium/calmodulin-dependent serine/threonine kinase, which has been reported to be a tumor suppressor with unbalanced expression in various tissues. However, its function in tumor immunotherapy is still unclear. The online GEPIA2 database was used to support TCGA results. We explored the DAPK1 pan-cancer genomic alteration analysis using the cBioPortal web tool. The Human Protein Atlas (HPA) was employed to mine DAPK1 protein information. We verified the expression of DAPK1 in lung adenocarcinoma samples using RT-qPCR. Subsequently, the relationship between the expression of DAPK1 and the clinical stage was analyzed. We used TIMER2.0 as the primary platform for studying DAPK1-related immune cell infiltration. Associations between DAPK1 and immunotherapy biomarkers were analyzed using Spearman correlation analysis. TMB and MSI expression was also examined. Finally, we used Kaplan-Meier Plots to evaluate the relationship between DAPK1 expression and the efficacy of immunotherapy. DAPK1 is aberrantly expressed in most cancer types and has prognostic power in various cancers. Gene mutation was the most common DAPK1 alteration across pan-cancers. The DAPK1 protein was mainly localized to tumor cell centrosomes. DAPK1 was also significantly associated with immune-activated hallmarks, immune cell infiltration, and the expression of immunomodulators. Notably, DAPK1 can also significantly predict responses to anti-PD1 and anti-CTLA-4 therapy in cancer patients. Our findings suggest that DAPK1 may not only be an effective prognostic factor in cancer patients but may also function as a promising predictive immunotherapy biomarker for cancer patients treated with immune checkpoint inhibitors.

Impact of the serum creatinine and cystatin C ratio for prediction of sarcopenia and prognosis in biliary tract cancer.

Sarcopenia is a poor prognostic factor in cancer patients. In recent years, there have been reports that serum creatinine and cystatin C (Cr/CysC) ratio is associated with sarcopenia. However, the prognostic value of the Cr/CysC ratio in biliary tract cancer is unclear. We evaluated the impact of the Cr/CysC ratio on sarcopenia and prognosis in biliary tract cancer. We retrospectively reviewed the records of 190 patients with biliary tract cancer who had undergone surgical resection from January 2017 to March 2023. Frozen serum samples collected at the time of surgery were used to measure CysC. We calculated the Cr/CysC ratio and investigated the relationship with sarcopenia and the prognostic significance. We calculated the cutoff value of the Cr/CysC ratio for low skeletal muscle index (SMI) (< 42cm2/m2 for males and < 38cm2/m2 for females). The optimal cutoff value of the Cr/CysC ratio was 0.848. The low Cr/CysC ratio group was significantly associated with higher preoperative CRP and lower albumin, lower SMI, lower handgrip strength, and higher intramuscular adipose tissue content. In multivariate analysis, patients with a low Cr/CysC ratio showed poorer overall survival (hazard ratio 2.60, 95% confidence interval 1.07-6.29, p = 0.033), which was significantly worse than in those with a high Cr/CysC ratio. In patients with biliary tract cancer, the Cr/CysC ratio showed weak correlation with sarcopenic indicators. However, the Cr/CysC ratio could be strong prognostic factor in biliary tract cancer.

Creatinine-to-cystatin C ratio and body composition predict response to PD-1 inhibitors-based combination treatment in metastatic gastric cancer.

Creatinine-to-cystatin C ratio (CCR) and body composition (BC) parameters have emerged as significant prognostic factors in cancer patients. However, the potential effects of CCR in gastric cancer (GC) remains to be elucidated. This multi-center retrospective study explored the predictive and prognostic value of CCR and BC-parameters in patients with metastatic GC receiving PD-1 inhibitors-based combination therapy. One hundred and thirteen GC patients undergoing PD-1 inhibitors-based combination therapy were enrolled at three academic medical centers from January 2021 to July 2023.A deep-learning platform based on U-Net was developed to automatically segment skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI). Patients were divided into two groups based on the median of CCR or the upper tertile of BC-parameters. Logistic and Cox regression analysis were used to determine the effect of CCR and BC-parameters in predicting response rates and survival rates. The CCR was positively correlated with SMI (r=0.43; P<0.001), but not with SATI or VATI (P>0.05). Multivariable logistic analysis identified that both low CCR (OR=0.423, P=0.066 for ORR; OR=0.026, P=0.005 for DCR) and low SATI (OR=0.270, P=0.020 for ORR; OR=0.149, P=0.056 for DCR) were independently associated with worse objective response rate (ORR) and disease control rate (DCR). Patients with low CCR or low SATI had significantly lower 8-month progression-free survival (PFS) rate and 16-month overall survival (OS) rate than those with high CCR (PFS rate, 37.6% vs. 55.1%, P=0.011; OS rate, 19.4% vs. 44.9%, P=0.002) or those with high SATI (PFS rate, 37.2% vs. 53.8%, P=0.035; OS rate, 8.0% vs. 36.0%, P<0.001). Multivariate Cox analysis showed that low CCR (HR=2.395, 95% CI: 1.234-4.648, P=0.010 for PFS rate; HR=2.528, 95% CI: 1.317-4.854, P=0.005 for OS rate) and low SATI (HR=2.188, 95% CI: 1.050-4.560, P=0.037 for PFS rate; HR=2.818, 95% CI: 1.381-5.752, P=0.004 for OS rate) were both independent prognostic factors of poor 8-month PFS rate and 16-month OS rate. A nomogram based on CCR and BC-parameters showed a good performance in predicting the 12- and 16-month OS, with a concordance index of 0.756 (95% CI, 0.722-0.789). Low pre-treatment CCR and SATI were independently associated with lower response rates and worse survival in patients with metastatic GC receiving PD-1 inhibitors-based combination therapy.

Impact of sarcopenia on recurrent biliary obstruction after EUS-guided biliary drainage in patients with malignant biliary obstruction.

Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD). The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO. Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76-12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events. Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS.

Different computed tomography parameters for defining myosteatosis in patients with advanced non-small cell lung cancer

Myosteatosis, excess muscle fat infiltration, is a novel prognostic factor in cancer patients. To define myosteatosis, skeletal muscle radiodensity (SMD) is most commonly used, while intramuscular adipose tissue (IMAT) is newly introduced. We aimed to compare SMD-defined and IMAT-defined myosteatosis for predicting overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) and to explore whether patients with both low SMD and high IMAT had a shorter OS than patients with low SMD or high IMAT alone. We consecutively and prospectively recruited adult patients with stage IIIB or IV NSCLC at a teaching hospital. The mean SMD of all skeletal muscle areas and the area of IMAT on the unenhanced chest computed tomography (CT) images at the 12th thoracic vertebral level were segmented using Mimics version 21.0. Myosteatosis was defined by either low SMD (SMD-defined myosteatosis) or high IMAT (IMAT-defined myosteatosis). The optimal cutoffs for low SMD and high IMAT were also determined using the maximally selected rank statistics method. We calculated hazard ratios (HRs) and the corresponding confidence intervals (CIs) to evaluate the associations of OS with low SMD, high IMAT, and a combination of them. We included 565 patients (345 men and 220 women; mean age 58.5±9.0 years). Lower IMAT exhibited a tendency toward a favorable prognosis in men (p=0.0015) and women (p<0.0001); whereas higher SMD tended to have a favorable prognosis in men (p=0.0006) and women (p<0.0001). At baseline, 423 (74.9%) participants had high IMAT, 432 (76.5%) participants had low SMD and 370 (65.5%) participants had both high IMAT and low SMD. Compared to those without either high IMAT or low SMD, the participants with either high IMAT or low SMD had a shorter OS, while the participants with both High IMAT and Low SMD had the shortest OS (log-rank p<0.0001). After adjustment for the same confounders, high IMAT (HR, 1.44; 95% CI, 1.10-1.87) and low SMD (HR, 1.92; 95% CI, 1.36-2.43) were separately associated with poor prognosis. Moreover, the combination of high IMAT and low SMD indicated a higher risk of poor prognosis (HR, 2.43; 95% CI, 1.62-3.66). Both SMD-defined and IMAT-defined myosteatosis are highly prevalent in patients with advanced NSCLC and may serve as independent prognostic factors for OS. The diagnosis of myosteatosis might consider a combination of low SMD and high IMAT because this would help identify patients at a higher risk of mortality.

Are Different Modes of Weight Loss Associated with Survival in Oropharyngeal Cancer?

Patients with oropharyngeal squamous cell carcinomas (OPSCC) often lose weight during radical radiotherapy (RT). Nutritional intervention is required in case of severe weight loss. However, weight loss does not provide full insight into body composition changes. Muscle mass is emerging as an important prognostic factor in cancer patients. We employed on-treatment cone-beam CT (CBCT) scans to monitor muscle mass and weight loss under the hypothesis that different modes of weight loss exist and may impact overall survival (OS). A retrospective analysis of 197 OPSCC patients treated with definitive or adjuvant (chemo)RT. Weekly weight measurements & CBCTs were collected. Patients were included if at least two time-points were available and the interval between the first and last was between 15-50 days. CBCTs were normalized to account for calibration differences between treatment machines. An in-house deep-learning model automatically segmented the skeletal muscle compartment at C3 on all CBCTs. Segmentations were visually checked and failures removed. Skeletal muscle volume (SMV, in mm3) was extracted after thresholding for intra-muscular fat. Relative changes in weight & SMV were then calculated. Linear models were fitted to each trajectory for every patient and slopes were estimated. The following weight & SMV categories were defined to generate equal groups: lost (more than 0.4 standard deviations (SDs) below the mean (M)), maintained (within +/- 0.4 SDs of M) or gained (more than 0.4 SDs above the M). Table 1 highlights the nine modes of body composition change. The prognostic value of these was investigated in multivariable Cox models accounting for age, sex, disease stage, oropharynx subsite, smoking status, performance status (PS), tumor p16 status, baseline weight & SMV, and treatment prescribed. The primary endpoint was OS. Mean weight & SMV changes during treatment were -0.047±0.001% & -0.044±0.019% per day. In multivariable analysis, gaining weight & losing SMV was identified as a significant risk factor for OS (p = 0.01, hazard ratio [95% CI]: 4.59 [1.40-15.10]). In this sub-group, mean weight & SMV change were +0.054±0.008% & -0.396±0.030% per day. PS>2 (p<0.001) & lower baseline weight (p = 0.02) were also significantly associated with OS. Patients losing substantial SMV but mildly gaining weight have significantly worse OS than others. This suggests there exists a group of patients where nutritional support is needed, but not offered because they maintain weight during treatment. Although our results need validation, continual monitoring of muscle condition during RT would allow these patients to be identified and promptly targeted for nutritional support.

Feasibility and safety of exercise during chemotherapy in people with gastrointestinal cancers: a pilot study

PurposeSarcopenia is a poor prognostic factor in cancer patients, and exercise is one of the treatments to improve sarcopenia. However, there is currently insufficient evidence on whether exercise can improve sarcopenia in patients with advanced cancers. This study examined the feasibility of exercise in advanced gastrointestinal (GI) cancer patients treated with palliative chemotherapy.MethodsBetween 2020 and 2021, 30 patients were enrolled in a resistance and aerobic exercise program for six weeks. The exercise intervention program (EIP) consisted of low, moderate, and high intensity levels. Patients were asked to select the intensity level according to their ability. The primary endpoint was the feasibility of the EIP measured by compliance during the six weeks. A compliance of over 50% was considered acceptable. The secondary endpoints were changes in weight and muscle mass, safety, quality of life (QoL) and overall survival (OS).ResultsThe median age of the study’s participants was 60 (30–77). The total compliance to the EIP was 63.3% (19/30 patients). Sixteen (53.3%) patients had a compliance of over 80%. The attrition rate was 30.0% (9/30). The mean exercise time was 41.4 min, and the aerobic exercise was 92.3% and the resistant exercise was 73.7%, and both exercise was 66.5%. Most patients performed the moderate intensity level exercises at home or near their home. The mean skeletal muscle index (SMI) was 43.5 cm2/m2 pre-chemotherapy and 42.2 cm2/m2 after six weeks of chemotherapy, with a decrease of -1.2 ± 2.8 cm2/m2 (-3.0%) (p = 0.030). In the poor compliance group, the mean SMI decrease was -2.8 ± 3.0 cm2/m2 which was significantly different (p = 0.033); however, in the good compliance group, the mean SMI decrease was -0.5 ± 2.5 cm2/m2 which was maintained over the six weeks (p = 0.337). The good compliance group had a significantly longer median OS compared with the poor compliance group (25.3 months vs. 7.9 months, HR = 0.306, 95% CI = 0.120–0.784, p = 0.014). The QoL showed a better score for insomnia (p = 0.042). There were no serious adverse events.ConclusionsThe EIP during palliative chemotherapy in advanced GI cancer patients showed good compliance. In the good compliance group, muscle mass and physical functions were maintained for six weeks. The EIP was safe, and the QoL was maintained. Based on this study, further research in exercise intervention in advanced cancer patients is needed.Clinical trial registrationThe clinical trial registration number is KCT 0005615 (CRIS, https://cris.nih.go.kr/cris/en/); registration date, 23rd Nov 2020.

Development and applicability of modified weight loss grading system in cancer: a real-world cohort study.

The original weight loss grading system (WLGS) was developed in western population, which did not perform effectively in cancer patients from China. This study aimed to develop and validate the modified WLGS (mWLGS) in the prognostic assessment of cancer patients in China. A prospective multicentre real-world cohort study involving 16842 patients diagnosed with cancer was conducted. Cox regression was used to calculate the hazard ratios for overall survival. Logistic linear regression was used to assess the odds ratio for 90-day outcomes. We calculated survival risks for the 25 mWLGS groups and clustered the approximate survival risks. Finally, we revised the prognostic grading system for mWLGS to include five grades of 0-4. Compared with the original WLGS, the mWLGS had a better prognostic differentiation effect in predicting the prognosis of patients with cancer. The survival rate gradually deteriorated with increasing grade of mWLGS, with the survival rate of grade 0 decreasing from 76.4% to 48.2% for grade 4 (76.4 vs. 72.8 vs. 66.1 vs. 57.0 vs. 48.2%, respectively). The mWLGS provides effective prognostic stratification for most site-specific cancers, especially lung and gastrointestinal cancers. High-grade mWLGS is independently associated with an increased risk of poor quality of life and adverse 90-day outcomes. Multivariate Cox regression analysis showed that the mWLGS was an independent prognostic factor for cancer patients in the validation cohorts. Compared with the original WLGS, the mWLGS can better stratify the prognosis of cancer patients. mWLGS is a useful tool for predicting survival, 90-day outcomes, and quality of life in patients with cancer. These analyses may provide new insights into the application of WLGS in cancer patients in China.

Liver-specific metastases as an independent prognostic factor in cancer patients receiving hospice care in hospital

BackgroundSurvival prediction is important in cancer patients receiving hospice care. Palliative prognostic index (PPI) and palliative prognostic (PaP) scores have been used to predict survival in cancer patients. However, cancer primary site with metastatic status, enteral feeding tubes, Foley catheter, tracheostomy, and treatment interventions are not considered in aforementioned tools. The study aimed to investigate the cancer features and potential clinical factors other than PPI and PaP to predict patient survival.MethodsWe conducted a retrospective study for cancer patients admitted to a hospice ward between January 2021 and December 2021. We examined the correlation of PPI and PaP scores with survival time since hospice ward admission. Multiple linear regression was used to test the potential clinical factors other than PPI and PaP for predicting survival.ResultsA total of 160 patients were enrolled. The correlation coefficients for PPI and PaP scores with survival time were -0.305 and -0.352 (both p < 0.001), but the predictabilities were only marginal at 0.087 and 0.118, respectively. In multiple regression, liver metastasis was an independent poor prognostic factor as adjusted by PPI (β = -8.495, p = 0.013) or PaP score (β = -7.139, p = 0.034), while feeding gastrostomy or jejunostomy were found to prolong survival as adjusted by PPI (β = 24.461, p < 0.001) or PaP score (β = 27.419, p < 0.001).ConclusionsAssociation between PPI and PaP with patient survival in cancer patients at their terminal stages is low. The presence of liver metastases is a poor survival factor independent of PPI and PaP score.

Abstract P3-05-52: Sarcopenia and Post-Mastectomy Breast Reconstruction Outcomes after Radiation Therapy

Abstract Background: Sarcopenia, characterized by the loss of muscle mass, has emerged as a negative prognostic factor in cancer patients. It has been associated with poorer outcomes and increased treatment-related morbidity. Post-mastectomy breast radiation therapy (RT) increases the likelihood of reconstructive complication, with up to 20% of reconstructed women requiring implant removal. The factors that lead to these complications are poorly understood and likely multifaceted. We investigated the relationship between pre-radiation therapy sarcopenia and post-mastectomy reconstruction outcomes. Methods: Chart review was performed to determine demographic, medical, and treatment variables, including reconstruction complication events and failures in breasts treated with mastectomy, immediate reconstruction, and RT. Reconstruction failure was defined as tissue expander or implant removal, resulting in no final reconstruction or autologous reconstruction only. Reconstruction complications included surgical site infection, late infection (1 year post-RT), seroma development, flap necrosis, nipple necrosis, wound dehiscence, capsular contracture, hematoma, extrusion, leak, venous congestion, and unplanned reoperation. An axial slice at the L2 or L3 vertebral body from the radiation therapy planning CT scan was analyzed for skeletal muscle area using a previously validated algorithm, with manual review and adjustment as indicated. Sarcopenia was defined by skeletal muscle index (SMI, skeletal muscle area in cm2 divided by patient’s height squared) below 34.4 cm2/m2. Chi-square, Kaplan Meier, and univariate Cox regression tests were used for analysis. Results: Ninety-nine women with breast cancer who underwent mastectomy, reconstruction, and RT were included in this study. All women had immediate reconstruction: 93 women had tissue expander placement while six women had permanent implant placement. Mean age was 47.5 years (SD 10.6) at diagnosis and median BMI was 24.8. Seventy-six percent were non-smokers, 24% were former smokers, and only 16 (16.2%) and 3 (3.0%) had hypertension or diabetes, respectively. Median follow-up was 2.7 years. Median SMI was 38 cm2/m2 and 18 (18%) met criteria for sarcopenia (SMI &amp;lt; 34.4 cm2/m2). Mastectomy was bilateral in 79 women, skin-sparing in 61, and nipple sparing in 31. Bilateral mastectomy was less frequent amongst women with sarcopenia (61%) compared to 84% of those without sarcopenia (p=0.03). After RT, twenty-three women required unplanned reoperation. Within these 23 women, there were 45 total complications. Complications included surgical site infection (n=18), capsular contracture (n=12), seroma (n=4), wound dehiscence (n=3), and others (n=8). However, only 8 women had reconstructive failure and none were sarcopenic at the time of the RT planning scan. Any complication or failure after RT occurred in similar proportions of patients with and without sarcopenia: 38% and 30%, respectively. Kaplan-Meier curves and univariate Cox regression models showed no significant difference in time to failure (p = 0.380) or time to any event (complication or failure) (p=0.53), between sarcopenic and non-sarcopenic patients. Conclusion: Sarcopenia, using SMI &amp;lt; 34.4 cm2/m2 on pre-radiotherapy planning scans, was not associated with an increased risk of post-radiotherapy reconstructive complication or failure in this selected cohort of non-smokers. Few women had sarcopenia at the time of operation, and results should be validated in a larger series. Citation Format: Yasamin Sharifzadeh, Robert Gao, William S. Harmsen, Jason Klug, Panagiotis Korfiatis, Kimberly Gergelis, Dean A. Shumway, Robert Mutter, Kimberly Corbin. Sarcopenia and Post-Mastectomy Breast Reconstruction Outcomes after Radiation Therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-52.

Serum Albumin Affects the Time-to-treatment Failure of Alectinib: A Multicenter Retrospective Study.

Alectinib is recommended for anaplastic lymphoma kinase fusion gene-positive non-small cell lung cancer. We have experienced early alectinib discontinuation due to disease progression and adverse effects in real world. Because alectinib has a high protein-binding rate of >99%, low serum albumin may increase the concentration of free drug and affect efficacy and adverse events. However, no association between serum albumin and the clinical impact of alectinib has been reported. The purpose of this study was to determine the effect of serum albumin on time-to-treatment failure (TTF) in alectinib. Fifty-six patients who were admitted to four hospitals (National Hospital Organization Hokkaido Cancer Center, Sapporo Minami-Sanjo Hospital, KKR Sapporo Medical Center, Otaru General Hospital) between October 2014 and September 2020 were retrospectively evaluated to identify those treated with alectinib. The multivariate analysis showed that the risk of discontinuation was significantly higher with serum albumin <3.6 g/dl compared to ≥3.6 g/dl at the start of alectinib administration (hazard ratio=3.00; 95% confidence interval=1.36-6.66; p<0.01). On Kaplan-Meier curves, TTF for serum albumin <3.6 was significantly shorter than that for ≥3.6. (median TTF: 12.1 months vs. not reach, p<0.01). To the best of our knowledge, this study is the first to report that serum albumin <3.6 g/dl at alectinib induction is associated with poor TTF. Low serum albumin is a poor prognostic factor in cancer patients. Thus, serum albumin levels must be measured before treatment.

A novel prognostic signature for lung adenocarcinoma based on cuproptosis-related lncRNAs: A Review

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease with complex pathogenesis, high mortality, and poor prognosis. Cuproptosis is a new type of programmed cell death triggered by copper accumulation that may play an important role in cancer. LncRNAs are becoming valuable prognostic factors in cancer patients. The effect of cuproptosis-related lncRNAs (CRlncRNAs) on LUAD has not been clarified. Based on the Cancer Genome Atlas database, CRlncRNAs were screened by co-expression analysis of cuproptosis- related genes and lncRNAs. Using CRlncRNAs, Cox and LASSO regression analyses constructed a risk prognostic model. The predictive efficacy of the model was assessed and validated using survival analysis, receiver operating characteristic curve, univariate and multifactor Cox regression analysis, and principal component analysis. A nomogram was constructed and calibration curves were applied to enhance the predictive efficacy of the model. Tumor Mutational Burden analysis and chemotherapeutic drug sensitivity prediction were performed to assess the clinical feasibility of the risk model. The novel prognostic signature consisted of 5 potentially high-risk CRlncRNAs, MAP3K20-AS1, CRIM1-DT, AC006213.3, AC008035.1, and NR2F2-AS1, and 5 potentially protective CRlncRNAs, AC090948.1, AL356481.1, AC011477.2, AL031600.2, and AC026355.2, which had accurate and robust predictive power for LUAD patients. Collectively, the novel prognostic signature constructed based on CRlncRNAs can effectively assess and predict the prognosis of patients and provide a new perspective for the diagnosis and treatment of LUAD.

101P Cachexia index and sarcopenia in patients with advanced gastrointestinal cancer treated with chemotherapy during exercise intervention

Sarcopenia is poor prognostic factor in cancer patients. The exercise intervention is one of the treatments to improve sarcopenia. The cachexia index (CXI) was developed to assess the degree of cancer cachexia. We estimated CXI in patients with advanced gastrointestinal cancer treated with palliative chemotherapy during exercise intervention.

Vimentin and tumor-stroma ratio for neoadjuvant chemoradiotherapy response prediction in locally advanced rectal cancer.

Vimentin expression in tumor tissues and the tumor-stroma ratio (TSR) have been demonstrated as strong prognostic factors for cancer patients, but whether they are predictive markers of neoadjuvant chemoradiotherapy (nCRT) outcome in locally advanced rectal cancer (LARC) patients is poorly understood. This study aimed to explore the predictive significance of vimentin and TSR combined for nCRT response in LARC patients. Imaging mass cytometry (IMC) was performed to determine the association of vimentin and TSR with nCRT response in six LARC patients [three achieved pathological complete response (pCR), three did not]. Immunohistochemistry (IHC) for vimentin and TSR on biopsy tissues before nCRT and logistic regression analysis were performed to further evaluate their predictive value for treatment responses in a larger patient cohort. A trend of decreased vimentin expression and increased TSR in the pCR group was revealed by IMC. In the validation group, vimentin [odds ratio (OR) 0.260, 95% confidence interval (CI) 0.102-0.602, p=0.002] and TSR (OR 4.971, 95% CI 1.933-15.431, p=0.002) were associated with pCR by univariate analysis. Patients in the vimentin-low/TSR-low or vimentin-high/TSR-high (OR 5.211, 95% CI 1.248-35.582, p=0.042) and vimentin-low/TSR-high groups (OR 11.846, 95% CI 3.197-77.079, p=0.001) had significantly higher odds of pCR. By multivariate analysis, only the combination of vimentin and TSR was an independent predictor for nCRT response (OR 9.324, 95% CI 2.290-63.623, p=0.006). Our study suggested that the combined assessment of vimentin and TSR can provide additive significance and may be a promising indicator of nCRT response in LARC patients.

Demoralization and Its Association with Quality of Life, Sleep Quality, Spiritual Interests, and Suicide Risk in Breast Cancer Inpatients: A Cross-Sectional Study.

With decreasing mortality, the quality of life, spiritual needs, and mental health of breast cancer patients have become increasingly important. Demoralization is a poor prognostic factor for cancer patients. The extent of demoralization in breast cancer patients and its association with these factors remains unclear. This cross-sectional study was conducted at a Taiwanese medical center. We enrolled 121 participants (34 with high demoralization and 87 with low demoralization, as per the Mandarin Version of Demoralization Scale). High demoralization was associated with reduced quality of life, sleep quality, and spiritual interests. Multivariate analyses revealed that the scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire ≥ 62.5 (OR = 0.21, p = 0.002) and Spiritual Interests Related to Illness Tool Chinese Version ≥ 3.66 (OR = 0.11, p < 0.001) were associated with low demoralization. Demoralized patients with depression had a poorer quality of life and sleep quality. Although not statistically significant, depressed and demoralized participants were at a higher risk of suicide. Cancer patients with both depression and demoralization had the worst prognosis. Breast cancer patients exhibited demoralization when they had unmet bio-psycho-social-spiritual needs. An early assessment of demoralization may improve holistic healthcare for breast cancer patients.

Is red blood cell distribution width a prognostic factor for colorectal cancer? A meta-analysis.

BackgroundRDW might be an easy and cost-effective pre-operative prognostic factor for cancer patients. The aim of the current study was to analyze whether red blood cell distribution width (RDW) was a prognostic factor for colorectal cancer (CRC) patients who underwent radical surgery.MethodsWe conducted the searching strategy in three databases including the PubMed, Embase and Cochrane Library from the inception to May 07, 2022, to find eligible studies. In this meta-analysis, we focused on the prognosis. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS).ResultsA total of seven studies involving 7,541 patients were included in this meta-analysis. After pooling up the HRs, red blood cell distribution width-coefficient of variation (RDW-CV) was not an independent prognostic factor of OS (HR = 1.48, I2 = 90%, 95% CI = 0.93 to 2.36, P = 0.10), however, red blood cell distribution width-standard deviation (RDW-SD) was an independent prognostic factor of OS (HR = 1.99, I2 = 0%, 95% CI = 1.59 to 2.49, P < 0.01). As for DFS, we found that RDW-CV (HR = 1.51, I2 = 83%, 95% CI = 0.94 to 2.43, P = 0.09 < 0.10) and RDW-SD (HR = 1.77, I2 = 56%, 95% CI = 0.91 to 3.43, P = 0.09 < 0.10) were both the independent prognostic factors. In terms of CSS, we found that RDW-CV was not an independent prognostic factor (HR = 1.23, I2 = 95%, 95% CI = 0.72 to 2.10, P = 0.46).ConclusionRDW-SD was an independent prognostic factor of OS and DFS, and RDW-CV was an independent prognostic factor of DFS.

Health and Lifestyle of Patients with Mesothelioma: Protocol for the Help-Meso Study

Patients with mesothelioma (PwM) have a poor prognosis and are at risk of adverse health outcomes and poor health-related quality of life. Sarcopenia and malnutrition are important prognostic factors for cancer patients and can be partially reversed with adequate nutrition and physical activity/exercise. There is a limited evidence base about the nutritional status of PwM, the understanding of which might potentially influence interventions in PwM. The primary aim of the Help-Meso (Health and Lifestyle of PwM) study is to describe the nutrition, appetite, physical activity and attitude towards lifestyle interventions of PwM. Patients, informal carers and health professionals will be invited to participate in semi-structured interviews and thematic analysis will be performed. The secondary aim of Help-Meso is to assess the feasibility of nutritional screening of PwM via a validated quantitative tool (Malnutrition Universal Screening Tool). The findings from this study will provide an understanding of the health and lifestyle of PwM and the corresponding attitudes of their informal carers and healthcare providers. This information will inform the design of future targeted interventions to improve the nutrition, quality of life of PwM and outcomes. The study has Research Ethics Committee (REC) and Health Research Authority approvals obtained from Wales REC7 (Integrated Research Application System (IRAS) project ID 287193).