Hormonal-Receptors-Positive and HER2-Negative Patients with Metastatic Breast Cancer Treated with First-Line Palbociclib and Hormonal Therapy: Impact of First-Cycle Neutropenia and Dose Reduction on Therapeutic Outcome.

Background: CDK 4/6 inhibitors with hormonal therapy are the standard first-line therapy in metastatic hormonal receptors (HR)-positive and HER2-negative breast cancer. This study aims to assess the impact of neutropenia with 1st cycle, dose reduction, HER2-low status, and other clinicopathological factors on survival outcomes with the first-line palbociclib and hormonal therapy. Patients and Methods. In this retrospective study, we recruited patients with metastatic HR-positive and HER2-negative breast cancer. Neutropenia with 1st cycle, palbociclib dose reduction in addition to different clinicopathological and survival data were checked in patients' medical records. Survival outcomes were compared according to the abovementioned factors. Results: We recruited 150 patients who received first-line palbociclib with hormonal therapy. 86% of patients developed 1st cycle neutropenia which was more common in patients with high Ki67. Dose reduction was recorded in 46.7% of patients and it was more common in patients with higher Allred scores (scores 7-8). The median progression-free survival (PFS) of the study group was 22 months. No significant difference was observed in PFS according to the 1st cycle of neutropenia or grade of neutropenia. Similarly, no difference in PFS according to palbociclib dose reduction and HER2 low status was observed. Only the Allred score and having a single site of metastasis had an independent significant relation with PFS. The median overall survival (OS) of the study group was 39 months. No significant difference was observed in OS according to the 1st cycle neutropenia, grade of neutropenia, palbociclib dose reduction, and HER2-low status. Only the Allred score and having a single site of metastasis had an independent significant relation with OS. In addition, no difference was observed in PFS and OS according to ECOG PS (2 vs. 0-1) or menopausal status. Conclusion: No significant impact of the 1st cycle neutropenia, dose reduction, having ECOG PS2, menopausal status, or HER2 low status on survival outcome was observed. Survival outcome was significantly better in patients with single metastatic sites and higher ER-Allred scores.

Assessment of compliance with hormonal therapy in early breast cancer patients with positive hormone receptor phenotype: A single institution study.

BACKGROUND: Adherence to long-term adjuvant hormonal therapy in hormonal receptors (HR)-positive breast cancer is really challenging and can affect the survival outcome. The present study aims to assess rate of compliance with hormonal therapy and possible predictive factors in a single institute in Saudi Arabia. PATIENTS &METHODS: We recruited patients with HR-positive breast cancer who presented to oncology outpatient clinics. Patients were assessed for compliance using a study questionnaire. Compliance was defined as taking ≥80% of prescribed doses of oral hormonal therapy. Different epidemiological, clinical, pathological and treatment data were checked in patients' medical records and correlated with compliance/interruption of hormonal therapy. RESULTS: Among the 203 recruited patients, 95.1% were compliant with hormonal therapy, while it was interrupted in 16.7% of patients, and 58.1% reported missing intake of hormonal pills. Age >50 years, having permanent job and higher education level were significantly associated with non-compliance in univariate analysis. On multivariate analysis, job status was the only independent predictor of non-compliance. The following parameters were significantly related to hormonal therapy interruption: marital status (single: 28.8% vs married patients: 12.6%, p = 0.01) and residence location (Makkah: 11.7% vs. outside Makkah: 25.3%, p = 0.019), lymphovascular invasion (LVI) (No: 20.9%, Yes: 7.8%, p = 0.025) and N0 tumours (compared to node-positive patients, p = 0.008). On multivariate analysis, marital status, residence location and N-stage, maintained significance relation with hormonal therapy interruption. CONCLUSION: Compliance with hormonal therapy was high in the study cohort. Marital status, residence location, job status and N-stage may be related to interruption/compliance with hormonal therapy.

Cost-Effectiveness of First-Line Cetuximab in Metastatic Colorectal Cancer in Saudi Arabia.

OBJECTIVES: Our objective was to evaluate the cost-effectiveness of first-line cetuximab in relation to primary tumor location and after resection from the perspective of the Saudi healthcare system over a lifetime horizon. METHODS: Two standard partitioned survival models were developed in this study comprising 3 health states in each model. The first model was to simulate outcomes and costs of folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus cetuximab compared with FOLFIRI alone in 2 target groups-first, in RAS wild-type left-sided metastatic colorectal cancer (mCRC) and second, in patients administered with 4 cycles of FOLFIRI plus cetuximab, who underwent a resection of liver metastases. The second model compared FOLFIRI plus cetuximab with FOLFIRI plus bevacizumab in wild-type left-sided mCRC and after resection. All cost data and utilities were extracted from published data. RESULTS: FOLFIRI plus cetuximab in RAS wild-type left-sided mCRC compared with FOLFIRI alone resulted in an incremental cost-effectiveness ratio of Saudi Riyal (SAR) 180 880 per quality-adjusted life-year (QALY) gained ($102 019; cost-effective). After resection of liver metastases, it resulted in SAR140 442 ($79 211) per QALY gained (cost-effective). When comparing FOLFIRI plus cetuximab with FOLFIRI plus bevacizumab, it resulted in SAR35 818 ($20 201) per QALY gained (highly cost-effective). After resection, it resulted in SAR109 612 ($61 822) per QALY gained (highly cost-effective). Thus, FOLFIRI plus cetuximab improved QALYs compared with FOLFIRI plus bevacizumab at the minimized difference in costs in left-sided mCRC and patients with unresectable metastases. CONCLUSION: FOLFIRI plus cetuximab is cost-effective compared with FOLFIRI plus bevacizumab or FOLFIRI alone in RAS wild-type left-sided mCRC and patients who undergo resection.

Profiling Activins and Follistatin in Colorectal Cancer According to Clinical Stage, Tumour Sidedness and Smad4 Status.

This study explored the roles of activins and follistatin in colorectal cancers. Paired malignant and normal colonic tissues were collected from archived paraffin-embedded (n = 90 patients) alongside fresh (n = 40 patients) specimen cohorts. Activin ß-subunits, follistatin and Smad4 mRNAs and proteins were measured by real-time PCR and immunohistochemistry (IHC). Mature activin-A, -B, -AB and follistatin proteins were measured by ELISA. Cancer tissues having ≤ the 20th percentile of the Smad4 IHC score were considered as low (L-S4) group. The Smad4-intact SW480 and Smad4-null HT29 colon cancer cell lines were treated with activins and follistatin, and cell cycle was analysed by flow cytometry. The cell cycle inducing (CCND1/CCND3) and inhibitory (p21/p27) proteins alongside the survival (survivin/BCL2) and pro-apoptosis (Casp-8/Casp-3) markers were measured by immunofluorescence. Thirty-nine patients had right-sided cancers (30%) and showed higher rates of L-S4 tumours (n = 17; 13.1%) alongside worse clinicopathological characteristics relative to left-sided cancers. The ßA-subunit and activin-A increased, whilst ßB-subunit and activin-AB decreased, in malignant sites and the late-stage cancers revealed the greatest abnormalities. Interestingly, follistatin declined markedly in early-stage malignant tissues, whilst increased significantly in the advanced stages. All activin molecules were comparable between the early stage right- and left-sided tumours, whereas the late-stage right-sided cancers and L-S4 tumours showed more profound deregulations. In vitro, activin-A increased the numbers of the SW480 cells in sub-G1 and G0/G1-phases, whereas reduced the HT29 cell numbers in the sub-G1 phase with simultaneous increases in the G0/G1 and S phases. The p21/p27/Casp-8/Casp-3 proteins escalated, whilst CCND1/CCND3/BCL2/survivin declined in the SW480 cells following activin-A, whereas activin-A only promoted p21 and p27 alongside reduced CCND3 in the HT29 cells. By contrast, activin-AB increased the numbers of SW480 and HT29 cells in Sub-G1 and G0/G1-phases and promoted the anti-cancer and reduced the oncogenic proteins in both cell lines. In conclusion, activins and follistatin displayed stage-dependent dysregulations and were markedly altered during the advanced stages of right-sided and L-S4 cancers. Moreover, the activin-A actions in CRC could be Smad4-dependent, whereas activin-AB may act as a Smad4-independent tumour suppressor protein.

Suggested Modifications to the Management of Patients With Breast Cancer During the COVID-19 Pandemic: Web-Based Survey Study.

BACKGROUND: Management of patients with cancer in the current era of the COVID-19 pandemic poses a significant challenge to health care systems. Breast cancer is the most common cancer internationally. Breast cancer is a disease that involves surgery, chemotherapy, hormonal therapy, targeted therapy, radiotherapy, and, more recently, immunotherapy in its management plan. The immune system requires months to recover from these medications, and this condition is even worse in patients with metastatic breast cancer who need ongoing treatment with these drugs. Some of these drugs, such as inhibitors of cyclin-dependent kinases 4 and 6, can cause rare but life-threating lung inflammation. Patients with breast cancer who have metastatic disease to the lungs can experience deterioration of disease symptoms with COVID-19 infection. Oncologists treating patients with breast cancer are facing a difficult situation regarding treatment choice. The impact that COVID-19 has had on breast cancer care is unknown, including how to provide the best care possible without compromising patient and community safety. OBJECTIVE: The aim of this study was to explore the views of oncologists regarding the management of patients with breast cancer during the COVID-19 pandemic. METHODS: A web-based SurveyMonkey questionnaire was submitted to licensed oncologists involved in breast cancer management in Saudi Arabia, Egypt, and United Arab Emirates. The survey focused on characteristics of the participants, infection risk among patients with cancer, and possible treatment modifications related to different types of breast cancer. RESULTS: The survey was completed by 82 participants. For early hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, 61 of the 82 participants (74%) supported using neoadjuvant hormonal therapy in selected patients, and 58% (48/82) preferred giving 6 over 8 cycles of adjuvant chemotherapy when indicated. Only 43% (35/82) preferred inhibitors of cyclin-dependent kinases 4 and 6 with hormonal therapy as the first-line treatment in all patients with metastatic HR-positive disease. A total of 55 of the 82 participants (67%) supported using adjuvant trastuzumab for 6 instead of 12 months in selected patients with HER2-positive breast cancer. For metastatic HER2-positive, HR-positive breast cancer, 80% of participants (66/82) supported the use of hormonal therapy with dual anti-HER2 blockade in selected patients. The preferred choice of first-line treatment in metastatic triple negative patients with BRCA mutation and programmed cell death 1 ligand 1 (PD-L1) <1% was poly(adenosine diphosphate-ribose) polymerase inhibitor according to 41% (34/82) of the participants, and atezolizumab with nab-paclitaxel was preferred for PD-L1 >1% according to 71% (58/82) of the participants. CONCLUSIONS: Several modifications in breast cancer management were supported by the survey participants. These modifications need to be discussed on a local basis, taking into account the local infrastructure and available resources.

Budget impact analysis of subcutaneous trastuzumab compared to intravenous trastuzumab in Saudi HER2-positive breast cancer patients.

Background: This study was aimed to assess the budget impact of SC trastuzumab compared to IV trastuzumab in patients with HER2-positive breast cancer (BC) from the perspective of the governmental health sector in Saudi Arabia, over a 3-year time horizon.Methods: A model was developed to calculate the direct medical and indirect costs for 394 incidents HER2-positive BC patients per year who would receive SC trastuzumab compared to IV formulation. We calculated drug acquisition costs for fixed, loading, and subsequent doses of trastuzumab. One-way sensitivity analysis was conducted.Results: Two scenarios were modeled: the first scenario evaluated the impact of gradual replacement of IV formulation by SC, the second scenario, evaluated impact of totally replacing IV formulation. The total annual costs in the first scenario were estimated to be SAR 177 million (USD 98 million) for IV trastuzumab compared to SAR 143 million (USD 79 million) for SC formulation, leading to a total budget saving of SAR 34,527,346 (USD 19,181,858). In the second scenario, the total annual costs were estimated to be SAR 108 million (USD 60 million) for SC trastuzumab compared to SAR 177 million (USD 98 million) for IV formulation, leading to budget savings of SAR 69,054,692 (USD 36,363,717).Conclusion: Benefits of the SC formulation over IV infusions are being converted to realistic monetary benefits for all providers and payers.

Virtual Management of Patients With Cancer During the COVID-19 Pandemic: Web-Based Questionnaire Study.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, patients with cancer in rural settings and distant geographical areas will be affected the most by curfews. Virtual management (telemedicine) has been shown to reduce health costs and improve access to care. OBJECTIVE: The aim of this survey is to understand oncologists' awareness of and views on virtual management, challenges, and preferences, as well as their priorities regarding the prescribing of anticancer treatments during the COVID-19 pandemic. METHODS: We created a self-administrated electronic survey about the virtual management of patients with cancer during the COVID-19 pandemic. We evaluated its clinical sensibility and pilot tested the instrument. We surveyed practicing oncologists in Gulf and Arab countries using snowball sampling via emails and social media networks. Reminders were sent 1 and 2 weeks later using SurveyMonkey. RESULTS: We received 222 responses from validated oncologists from April 2-22, 2020. An awareness of virtual clinics, virtual multidisciplinary teams, and virtual prescriptions was reported by 182 (82%), 175 (79%), and 166 (75%) respondents, respectively. Reported challenges associated with virtual management were the lack of physical exam (n=134, 60%), patients' awareness and access (n=131, 59%), the lack of physical attendance of patients (n=93, 42%), information technology (IT) support (n=82, 37%), and the safety of virtual management (n=78, 35%). Overall, 111 (50%) and 107 (48%) oncologists did not prefer the virtual prescription of chemotherapy and novel immunotherapy, respectively. However, 188 (85%), 165 (74%), and 127 (57%) oncologists preferred the virtual prescription of hormonal therapy, bone modifying agents, and targeted therapy, respectively. In total, 184 (83%), 183 (83%), and 176 (80%) oncologists preferred to continue neoadjuvant, adjuvant, and perioperative treatments, respectively. Overall, 118 (53%) respondents preferred to continue first-line palliative treatment, in contrast to 68 (30%) and 47 (21%) respondents indicating a preference to interrupt second- and third-line palliative treatment, respectively. For administration of virtual prescriptions, all respondents preferred the oral route and 118 (53%) preferred the subcutaneous route. In contrast, 193 (87%) did not prefer the intravenous route for virtual prescriptions. Overall, 102 (46%) oncologists responded that they would "definitely" prefer to manage patients with cancer virtually. CONCLUSIONS: Oncologists have a high level of awareness of virtual management. Although their survey responses indicated that second- and third-line palliative treatments should be interrupted, they stated that neoadjuvant, adjuvant, perioperative, and first-line palliative treatments should continue. Our results confirm that oncologists' views on the priority of anticancer treatments are consistent with the evolving literature during the COVID-19 pandemic. Challenges to virtual management should be addressed to improve the care of patients with cancer.

Suggested modifications in oncology/hematology inpatient service in Saudi Arabia during coronavirus disease-2019 (COVID-19) pandemic.

BACKGROUND: Management of cancer patients in the current era of coronavirus disease-2019 (COVID-19) pandemic poses significant challenges on health-care systems. However, it is mandatory to keep the required level of care of cancer patients while taking the necessary precautions to maintain the safety of both patients and health-care professionals (HCPs). The present survey explores suggested modifications of inpatient oncology/hematology care during the COVID-19 pandemic. MATERIALS AND METHODS: A web-based questionnaire using SurveyMonkey was distributed to HCPs taking care of inpatient hematology/oncology service including oncologists, hematologists, and inpatient nurses in Saudi Arabia. The 25 items selected for the survey focused on five domains including characteristics of HCPs, COVID-19 infection risk among admitted patients, possible modifications related to physicians/nursing practice, and suggested infection control measures. Clinical sensibility assessment was conducted to evaluate the comprehensiveness, clarity, and face validity of our instrument on a scale of 1-5. The percentages of HCP responses to the suggested modifications in the survey were assessed in descriptive statistics to summarize data and report views of participants. RESULTS: Of 215 HCPs, 195 responded and completed the survey. Of the respondents, 30.4% were medical oncologists, whereas hematologists and nurses constituted 6.7% and 62.9% of the participants, respectively. The majority of respondents (87.6%) work in governmental hospitals. The majority of participants (82%) have diagnosed patients with COVID-19 in their hospitals and modifications in inpatient practice during the COVID-19 pandemic were supported by 95% of respondents. The supported modifications by participants include enhanced use of oral medications (83.5%), phone calls to admitted stable patients by physicians, instead of physical interview (77%), decreasing frequency of vital signs assessment in stable patients (91%), decreasing the duration of stay in patients rooms (89%), using peripheral instead of central lines (76%), using video-based educational materials to patients through hospital TV network (91%), testing for COVID -19 before scheduled radiology imaging and procedures (74%), and performing routine nasopharyngeal swabs for HCPs (67%). CONCLUSION: Several modifications in inpatient oncology/hematology practice were supported by the survey participants. These suggestions need to be discussed on local basis considering local infrastructure, available resources, and level of required care.

Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.

PURPOSE: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). MATERIALS AND METHODS: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. RESULTS: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI= 1.28-13.16, p=0.018) and a lower pathological stage (OR =3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI= 1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. CONCLUSIONS: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

Thyroid transcription factor-1 expression in advanced non- small cell lung cancer: impact on survival outcome.

BACKGROUND: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (≤60 vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. RESULTS: A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7 months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed-containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs 5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS. Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were predictors of worse OS. CONCLUSIONS: Pemetrexed-containing therapy significantly improved PFS while OS was improved in EGFR mutant patients. Female patients had better PFS and OS. TTF1 expression was not a prognostic marker in advanced non-squamous NSCLC.

Prognostic value of mammographic breast density in patients with metastatic breast cancer.

Breast density is a modifiable trait linked with breast cancer predisposition. However, the relation between mammographic breast density and survival outcome is not yet clarified. The present study aims to study the prognostic value of mammographic density in patients diagnosed with metastatic breast cancer. In this observational study, breast cancer patients with metastatic disease at diagnosis were enrolled. Two-view mammograms were performed at diagnosis, and breast density was quantitatively assessed. Progression-free survival (PFS) was correlated with breast density and other prognostic variables in univariate and multivariate analyses. PFS, stratified by different prognostic factors, was assessed in low compared to high density patients to check for possible differential survival outcome in patients' subgroups. Among the sixty enrolled patients, median PFS in low density patients was significantly better than those with high density (18.4 months, 95 % CI 14.88-22.15 vs. 9.3 months, 95 % CI 8.51-13.60, respectively, p = 0.002). Significant correlation of breast density with PFS persisted after adjustment by body mass index (p = 0.003) and after multivariate analysis incorporating other prognostic variables (HR 6.16, 95 % CI (2.17-17.48), p = 0.001). PFS was better in low density patients older than 40 years at diagnosis (p = 0.001), with HER2-negative disease (p = 0.015), hormonal receptor-positive phenotype (p = 0.020), patients with single site of metastasis (p = 0.006), and patients with bone-only metastases (p = 0.042). Breast density assessed at the time of diagnosis was significantly correlated with PFS of metastatic breast cancer patients. Survival outcome is improved in certain patients' subgroups with low breast density.

Clinico-pathological patterns and survival outcome of colorectal cancer in young patients: western Saudi Arabia experience.

BACKGROUND: The prognosis of young colorectal cancer (CRC) patients has been addressed by several studies but with contradictory results. The aim of the present study was to evaluate the clinico-pathological features of young Saudi patients with CRC in addition to displaying their survival outcome. MATERIALS AND METHODS: In this retrospective study, young CRC patients (≤ 40 years) diagnosed between 2007 and 2011 from 4 centres in western Saudi Arabia, were included. Clinico-pathological features, tumor markers, dates of disease relapse and death were collected. Survival parameters were compared with those of older Saudi patients, reported in previous studies. RESULTS: One hundred and sixteen young patients with CRC were identified (32.2% rectal, 67.8% colon). Some 44% were metastatic while 32.7% had stage III at diagnosis. Patients with grade 3 tumors made up 29.4% of the total while 49.5% had positive lymphovascular invasion (LVI), 56% had a lymph node (LN) ratio ≥ 0.2 and 40.2% were K-ras mutant. Median disease-free survival (DFS) and overall survival (OS) in non-metastatic cases were 22.8 and 49.6 months respectively with better median DFS in K-ras wild compared to mutant patients (28.5 vs 20.9 months, p=0.005). In metastatic cases, median OS was 19.5 months. These survival outcomes are inferior compared to those of older Saudi patients reported in prior studies. CONCLUSIONS: Young CRC patients present more commonly with advanced stage and a high incidence of adverse prognostic factors such as LVI and high LN ratio. Young CRC patients seem to have worse survival compared to older Saudi patients.

Phase II study of low-dose fixed-rate infusion of gemcitabine combined with cisplatin and dexamethasone in resistant non-Hodgkin lymphoma and correlation with Bcl-2 and MDR expression.

This study aims to assess the efficacy of low-dose fixed-rate infusion of gemcitabine, cisplatin and dexamethasone in resistant non-Hodgkin lymphoma (NHL) patients in addition to evaluating the prognostic value of B cell lymphoma 2 (Bcl-2) and multidrug resistant (MDR) expression in this cohort of patients. Patients with relapsed/refractory NHL following at least two chemotherapy regimens were enrolled. They received gemcitabine 800 mg/m2 in fixed infusion rate of 10 mg/m2/min, cisplatin 35 mg/m2 in days 1, 15 and dexamethasone 20 mg days 1-4, 15-18 every 28 day. Response to treatment, time to disease progression (TTP) and 1-year progression-free survival (PFS) were assessed together with their association with Bcl-2, MDR expression and other prognostic variables. Overall response to treatment was 32% (14% complete response). Median TTP and 1-year PFS were 2 months and 31.3%, respectively. Predictors of response to treatment were early stage [odd ratio (OR)=4.6, 95% CI 1.3-16.4], low/low intermediate International Prognostic Index (IPI) (OR=6.2, 95% CI 1.2-31.7), negative/low Bcl-2 expression (OR=6.2, 95% CI 1.2-31.7) and negative/low MDR expression (OR=18, 95% CI 1.4-28.9). However, IPI status lost its value in multivariate analysis. TTP and 1-year PFS were significantly associated with Bcl-2 expression (p=0.04), tumor status before enrollment (relapse vs. refractory, p<0.0001) and tumor stage (p<0.000). In multivariate analysis, clinical stage was the only predictor of TTP and 1-year PFS. Fixed-rate gemcitabine infusion with cisplatin and dexamethasone had reasonable activity in resistant NHL. Clinical stage, Bcl-2 and MDR expressions were predictors of response to treatment, while only clinical stage was associated with TTP and 1-year PFS.

Triple-negative breast cancer: future prospects in diagnosis and management.

Triple-negative breast cancer (TNBC) is an aggressive subtype comprising about 10-20 % of breast cancer patients with an overall poor prognosis. Recently, it was found to be a heterogeneous disease that has been classified into six subtypes based on molecular signature. In preclinical trials, these subtypes have different active signaling pathways with variable response to chemotherapy. To improve treatment outcome of TNBC, therapy should be tailored according to the active driving signaling aberration. Molecular testing represents the optimal way to stratify patients, but it has some difficulties to be implemented in routine clinical practice. This article provides an assumption for stepped diagnostic algorithm of TNBC based on immunohistochemistry markers in addition to a suggested tailored therapeutic strategy for advanced TNBC based on the driving aberrations. Furthermore, most TNBC patients develop early relapse despite adjuvant chemotherapy. We provide a design for future adjuvant therapy for the disease. This design is based on targeting proposed active pathways in breast cancer stem cells responsible for regenerating the tumor and disease relapse. Finally, we provide a proposed design for future clinical trials in TNBC to allow for investigation of different medications in this heterogeneous disease based on upfront patient stratification and then allocation to the suitable treatment arms.

Prediction of in-hospital mortality of patients with advanced cancer using the Chuang Prognostic Score.

The prediction of in-hospital mortality may help in improving end-of-life care for patients dying of cancer. The Chuang Prognostic Score (CPS) was developed to predict survival of terminally ill patients with cancer. The CPS was assessed in 61 hospitalized adult patients with advanced cancer. Using a CPS cutoff point of ≥6, in-hospital mortality was predicted with 71% positive predictive value, 91% negative predictive value, 75% sensitivity, 89% specificity, and 85% overall accuracy. The patients were divided according to the CPS score into 3 groups (Group 1: CPS < 3.5, Group 2: CPS ≥ 3.5-<6, and Group 3: CPS ≥ 6) with a median survival of not reached, 118 days, and 16 days, respectively (P < .001). The CPS may be useful in predicting in-hospital mortality of hospitalized patients with advanced cancer.