Biochemical outcome in metastatic prostate cancer patients following prostate-directed radiotherapy.

Background: The role of cytoreductive local radiotherapy (RT) in metastatic prostate cancer (mPCa) has recently been established. This study aimed to evaluate the biochemical outcome of local RT in mPCa. Methods: This randomised controlled phase III study was conducted at the Clinical Oncology Department, Suez Canal University Hospital. Eligible participants were de-novo or metachronous mPCa patients with Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomised to receive either cytoreductive prostate-directed RT in addition to standard care or standard care alone. The conventional radiation schedule of 70 Gy/35 fractions or the hypofractionated schedule of 55 Gy/20 fractions were delivered. The primary endpoint was biochemical progression-free survival (BPFS), and the secondary endpoint was overall survival (OS). Survival and post-hoc analyses were performed using Cox regression and the Kaplan-Meier method with the log-rank test. Results: Between 23 November 2020 and 21 2022, 70 patients were enrolled in this study. Of them, 34 patients were assigned to the prostate RT group, and 29 patients were assigned to the control group. At a median follow-up of 12 months, the median BPFS has not been reached for the prostate RT group compared to 4.067 months for the control group (HR: 0.147, p < 0.001). Subgroup analysis showed that the median BPFS was statistically significantly correlated with low-volume (95% CI, 0.004 to 0.262, p = 0·001) and hormonal-sensitive metastatic disease (95% CI, 0.010 to 0.192, p < 0·001). The median OS was 16.33 months for the prostate-RT group compared to 11.33 months for the control group (HR: 0.313, p = 0.003). Conclusion: Prostate-directed RT improved BPFS and OS in mPCa patients, particularly in those with low volume and hormonal-sensitive disease. Trial Registration: This trial is registered on (27/4/2023), retrospectively registered with pactr.samrc.ac.za, PACTR202305854600529, URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25510.

Health-related quality of life of metastatic prostate cancer patients treated with prostate Radiotherapy.

BACKGROUND: The impact of prostate radiotherapy on patient-reported health-related quality of life (HRQoL) significantly influences the outcomes of metastatic prostate cancer. We measured and compared HRQoL of metastatic prostate cancer patients who received cytoreductive prostate radiotherapy. METHODS: Between November 23, 2020, and November 21, 2022, we recruited 70 metastatic prostate cancer patients at the Department of Clinical Oncology at Suez Canal University Hospital. Patients were eligible if they had synchronous and metachronous histopathological confirmed metastatic adenocarcinoma and an Eastern Cooperative Oncology Group performance status ≤ 2. Random allocation was performed for either definitive local radiotherapy concurrent with the standard androgen deprivation therapy (ADT) or to the standard ADT alone. Definitive radiotherapy was delivered conventionally (70 Gy/35 fractions) or through the hypofractionated regimen (55 Gy/20 fractions). Patients completed the comprehensive European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PR25) at baseline, then at three-month intervals for one year. The primary endpoint was patient-reported HRQoL, with secondary endpoints including toxicity and radiographic progression-free survival (rPFS). Mean HRQoL scores between groups were compared using the independent samples t-test. RESULTS: We observed clinically significant improvements in urinary and bowel functions between baseline, 3-month, 6-month, and 12-month intervals after receiving definitive prostate radiotherapy. Patients in the radiotherapy group had significantly lower urinary symptoms scores than the control group. However, sexual activity and functioning showed significant deterioration. CONCLUSION: Cytoreductive prostate radiotherapy in metastatic prostate cancer patients significantly improved urinary functioning, preserved bowel functioning but was associated with worsening of sexual functioning. TRIAL REGISTRATION: This trial was registered on (27/04/2023) with pactr.samrc.ac.za, PACTR202305854600529, URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25510 .

The application of the Glasgow prognostic score to predict the survival in patients with metastatic pancreatic carcinoma.

Objectives: Thither is a more pressing effort to think about chemotherapy (CTx) in second-line and beyond in patients with metastatic pancreatic cancer (mPC). The current work aimed to evaluate the value of the Glasgow prognostic score (GPS) and modified Glasgow prognostic score (mGPS) to predict the survival in patients receiving second-line CTx protocol. Material and Methods: We retrospectively reviewed the patients' medical files with mPC who received second-line CTx protocol between September 2013 and December 2017. The GPS/mGPS graded from 0 to 2 based on C-reactive protein and serum albumin. Results: One hundred and sixty-nine patients with mPC were eligible. Survival of patients with Score 0 (GPS/mGPS) was better than that of Score 1 (GPS/mGPS) or Score 2 (GPS/mGPS), which was statistically significant (P < 0.001). Of 78 patients who died, only 16 patients belonged to Score 0 (GPS/mGPS), compared to 30 patients belonged to Score 1 (GPS/mGPS) and 32 patients belonged to Score 2 (GPS/mGPS). Univariate analysis showed that high GPS/mGPS (P < 0.000) as well as poor Eastern Cooperative Oncology Group Performance Status (P < 0.000) and metastasis either to the liver (P < 0.01) or lung (P < 0.04) were linked with worse prognosis. A statistically significant association was detected between the two scores. Cohen's Kappa coefficient (k) was 0.9, SD = 0.03; 95% CI (0.787-0.922; P < 0.001). Conclusion: Our data suggested that GPS/mGPS is an easy and applicable index that may be used in daily practice and may help in the prognostic stratification of mPC patients to avert overtreatment in frail patients and raise the best supportive treatment concept.

Prediction of Survival Outcome Using Chuang's Prognostic Scale in Metastatic Breast Cancer.

BACKGROUND: For physicians and patients, survival estimation is vital for the treatment plan, especially with frequent use of new therapeutic agents in metastatic breast cancer (MBC). The Chuang's Prognostic Scale (CPS) is a validated prognostic score that may be useful in the avoidance of unnecessary palliative systemic treatment. AIM: The present study aimed to evaluate the CPS in survival prediction in patients with MBC after at least two lines of palliative systemic chemotherapy protocols (PSCPs). METHODS: CPS was prospectively measured in 221 patients with MBC. The total score ranged from 0 to 8.5; the lower score refers to a good prognosis. The survival assessment was made by the Kaplan-Meier curve and the survival difference among the groups was estimated by log-rank test. RESULTS: Using the cutoff value of CPS 5.7, the patients were classified into two groups: Group A had score ≤5.7 (174 patients, 78.7%) and Group B had CPS score >5.7 (47 patients, 21.3%). About 86.2% of the patients in Group A survived >3 months (median survival was 165 days, 95% confidence interval [CI]: 77-261) compared with 21.3% of patients survived in Group B (median survival was 81 days, 95% CI: 55-123) (P = 0.00). The sensitivity, specificity, positive predictive value, and negative predictive value were 97.6% (95% CI: 87.4-99.9), 98.3% (95% CI: 95.2-99.7), 93.2% (95% CI: 81.6-97.7), and 99.4% (95% CI: 96.2-99.9), respectively, for the 3-month mortality prediction. CONCLUSION: CPS could be helpful in estimating the survival outcome in patients with MBC who received at least two PSCPs.

The effect of body mass index on clinico-pathological features and survival outcome in metastatic bladder carcinoma.

OBJECTIVES: The The study proposed to assess the relation between the body mass index (BMI) and clinicopathological features of metastatic urinary bladder cancer (uBCa) and the influence on survival outcome. METHODS: A retrospective study included 201 metastatic uBCa patients. They classified into three groups according to BMI, group I; a BMI of 18.5-24.9 kg/m2, group II; a BMI of 25-29.9 kg/m2, and group III; BMI ≥ 30 kg/m2. The Kaplan - Meier curve used for survival analysis. RESULTS: 69 patients (34.3%) belonged to group I, 75 patients (37.3%) belonged to group II, and 57 patients (28.4%) belonged to group III. Smoking history was detected in 44.8% of patients with Performance Status (PS) 0 in 55.2%, and PS 1 in 26.9%. Of note, 44.8% of patients responded to 1st chemotherapy and 50.7% received more than 2 lines. Through the univariate analysis, poor prognostic outcome was associated with male (P= 0.01), smoking (P=0.002), BMI group II and group III (p=0.00), PS 2 compared with PS 0 (P<0.001), metastasis to liver, lung, and lymph node (P<0.001), and no response to first line chemotherapy (P<0.001). While no effect for age (P=0.1), bone metastasis (P=0.6), serum LDH (P=0.1), serum albumin (P=0.4), and ≥2 chemotherapy lines (P=0.5) on survival outcome. After the follows-up period, the OS was 12.7 months for all patients. Regarding the BMI groups, the median OS was 23.5 months, 12.9 months, and 10.2 months for group I, group II, and group III respectively (p<0.001). CONCLUSION: High BMI associated with aggressive clinico-pathological features and poor survival outcome in metastatic uBCa.

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response.

BACKGROUND: There is growing evidence that the response to chemotherapy may be affected by Androgen Receptor (AR) expression suggesting that triple-negative breast cancers (TNBC) AR+ and quadruple negative breast cancer (QNBC) subtypes may have different diseases behavior. METHODOLOGY: We retrospectively estimated the predictive value of the AR expression in stage II and stage III TNBC patients treated with neoadjuvant chemotherapy (NAC) and correlated with the rate of pathological response (pCR). RESULTS: Of 89 TNBC patients, 29 patients (32.6%) were TNBC AR+ and 60 patients (67.4) were QNBC. Most of the patients were less than 60 years old. Of note, approximately 62% in the QNBC group were less than 40 years old compared with 39 % in the TNBC AR+ group. The Ki-67 expression was higher in the QNBC in comparison with TNBC AR+ being 86.7% and 65.5%, respectively. QNBC subgroup showed higher rates of pCR compared with TNBC; 60% and 24%, respectively. Higher Ki-67 expression, higher grade, and lymph node involvement were statistically significantly correlated with the rate of pCR in the QNBC group (p=0.02, p=0.04, and p=0.03, respectively). In contrast, no significant association was observed between pCR and clinical-pathological features in the TNBC AR+ group. CONCLUSION: Our results suggested that the AR expression in TNBC may be applied as a predictive marker for NAC. TNBC AR+ had a lower rate of pCR compared with QNBC, suggesting that this subtype may have a partial chemoresistance.

Impact of Prognostic Nutritional Index on Terminal Cancer Patients.

BACKGROUND: In terminal cancer patients (TCPs), one of the most important things is to define the survival to help the main responsible physicians, patients, and main caregivers make decisions, set goals, and work across the end-of-life strategies. PATIENTS AND METHODS: We retrospectively reviewed the medical files of TCPs, who died during September 2011 and December 2017, to recognize the correlation between prognostic nutritional indices (PNIs) and survival in those subtypes of patients. The receiver operating characteristic (ROC) curve was used to identify the cutoff value of PNI. RESULTS: A total of 858 TCPs were eligible and included, the median age was 62 years (range: 18-107). The most common primary cancer sites were colorectal cancer in 151 patients (17.6%), hepatobiliary in 129 (15%), lung cancer in 115 (13.4%), breast cancer in 114 (13.3%), and genitourinary in 80 (9.3%). The mean value of PNI for all cancer types was 32.9 ± 6.7. The values showed different levels across cancer types. For patients who lived >2 weeks, PNI was 36.7 compared with that who died within 2 weeks was 29.3, which was a statistically significant (P < 0.001). By the ROC curve, the cutoff value of PNI was 32.3 and area under the curve was 0.888. The sensitivity, specificity, positive predictive value, and negative predictive value were 91.28% (95% confidence interval [CI]: 88.2-93.8), 71.09% (95% CI: 66.5-75.4), 76.5% (95% CI: 73.7-79.2), and 88.8% (95% CI: 85.3-91.5), respectively. CONCLUSION: The PNI is an easy and an applicable biomarker to estimate life expectancy in TCPs.

Aggressive Care at the End of Life; Where Are We?

BACKGROUND: Although, efforts to encourage palliative care only for terminal patients, aggressive end-of-life care (EOL) care still common for those probably to die shortly. AIM: Multicenter experiences to investigate where did we stand in this era? PATIENTS AND METHODS: A retrospective study included patients with advanced solid tumors. The presence of one or more of the following indicators in the last month of life (LM) referred to aggressive EOL care: emergency department (ED) visits ≥ twice, admission to the hospital through ED, death in critical care units (CCUs), and palliative chemotherapy (PC) at the past 2 weeks before death. RESULTS: A total of 435 patients, 51.5% were men with a median age of 62 years (range: 17-108), were included in the study. Most of the patients (89.2%) belonged to Group II; they had attended ED at least twice (60%), approximately 53% admitted to the hospital through ED, 31% received PC-LM with 41% of them had at the past 2 weeks before death, 13% died in the CCUs, and more than half of them (53%) survived <2 weeks. Kaplan-Meier estimator revealed that median survival was 30 days in Group I versus 13 days in Group II (odds ratio: 1.63; 95% confidence interval: 1.20-2.21; P = 0.002). The median survival was statistically significantly associated with PC-LM ≥14 days and the admission mode. There was no statistically significant association with age, sex, and primary cancer sites. CONCLUSION: The majority of our patients continue with anticancer treatments they possibly do not need and associated with poor survival.

CDK4/6 inhibitors in advanced breast cancer, what is beyond?

Resistant to hormonal treatment considered the main clinical challenge in the management of advanced breast cancer (ABC). The use of CDK4/6 inhibitors (CDK4/6I) may change the treatment landscape. In this mandated review, we will focus on the applicable role of CDK4/6I in the management of HR+/HER2- ABC, mechanisms of resistance, and promising future implementation.

C-MYC and BCL2: Correlation between Protein Over-Expression and Gene Translocation and Impact on Outcome in Diffuse Large B Cell Lymphoma

Background: Due to lack of availability of gene expression profiling (GEP) for most developing countries and clinicians; the immunohistochemistry (IHC) is mostly used in the clinical application. The aim of our study is to check the possibility of using IHC to detect MYC and BCL2 in our patients with diffuse large B-cell lymphoma (DLBCL) instead of GEP to stratify them into high and low-risk groups. This will help in a proper treatment choice of subsequent improvement in the survival outcome. Method: During the study period, 90 DLBCL patients were eligible. MYC and BCL2 evaluated by IHC and gene rearrangement by real-time PCR (RT-PCR) and correlated with clinical-pathological features and survival. Results: Through IHC, the expression of MYC, BCL2, and double expression was detected in 35.6%, 46.7% and 30% of patients, respectively. While by RT-PCR, it was 4.53±0.74 for MYC compared with 2.18±0.78 for BCL-2. Most patients with BCL2+/MYC+; double-expressor and double-hit lymphomas (DEL and DHL) had high stage (III, IV), more extra-nodal involvement, (P value <0.001) and intermediate to high International Prognostic Index (IPI) risk profile (P-value <0.001). The median overall survival was 14 months and 6 months for DEL and DHL, respectively. While all patients with DHL died during the follow-up period, the median PFS were only 2 months for DEL. There was a statistically significant correlation between mRNA of MYC and BCL2 with their protein expression (p<0.001). Conclusion: Our results confirmed the unique characters and poor outcome associated with DEL and DHL mandated the need for more intense therapy and not the standard protocol. Moreover, the significant correlation between protein overexpression and gene rearrangement may open the door for the possibility to use IHC instead of RT-PCR in developing countries.