Clinico-pathologic profile and clinical outcomes of patients with indolent lymphoma at the Cancer Institute of the Philippine General Hospital: A seven-year experience

INTRODUCTION: Indolent lymphoma (IL) is a slowly growing lymphoma, generally refractory to conventional chemotherapy. There are several types of IL, which includes follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and waldenstrom macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL). Presently, there are no known data in the Philippines on IL. This study is done to determine the clinico-pathologic profile and outcomes of Filipino patients with IL. METHODS: This study is a retrospective chart review of outpatient department cases of IL seen at the Philippine General Hospital-Cancer Institute from January 2009 to January 2016. The following were documented: age; gender; primary location; presence or absence of B symptoms; type of IL; Ann-arbor stage; prognostic indices for FL and MCL; and staging with bone marrow aspiration and whole body CT scan. Treatment intervention and clinical outcomes were documented. RESULTS: This study showed that SLL was the most common IL. Most were elderly (>40 years old); male; lacked B symptoms; limited disease; and primary location at or near the orbital area. MCL were seen in all risk groups. Follicular lymphoma (FL) were mostly low risk and had grade one histology. Majority had disease control regardless of treatment intervention. Most patients with recurrence/progression after initial treatment had limited disease but were understaged. Most of the patients were not staged with bone marrow aspiration or whole body computed tomography. CONCLUSION: The results of this study are mostly consistent with known literature on IL. Absence of B symptoms and limited disease may indicate a low-grade histology. Observation was the most common option for asymptomatic patients.  

Bevacizumab in HER2neu negative locally recurrent and metastatic breast cancer: The BHerN review

INTRODUCTION: A promising strategy for HER2-negative metastatic breast cancer (mBC) is to target the veascular endothelial growth factor receptor using bevecizumab. Several randomized controlled trials (RCTs) have consistently demonstrated improvement in progression-free survival (PFS).METHODS: This meta-analysis was undertaken to determine the added benefit of bevacizumab (BV) to chemotherapy in HER2-negative locally recurrent and mBC. RCTs that compared the efficacy and safety of BV+chemotherapy to placebo+chemotherapy in the first- or second-line setting were selected. The primary outcome was PFS. The secondary outcome measures were overall survival (OS) and objective response rate (ORR). Analysis of safety was done by pooling grades 3-5 toxicities. Four RCTs were included in the meta-analysis: E2100, AVADO, RIBBON-1, and RIBBON-2.RESULTS: The use of BV+chemotherapy showed statistically significant improvement in PFS (HR 0.73 [0.65, 0.82] 95% Cl, pCONCLUSION: BV prolongs PFS and increases ORR in patients with HER2-negative locally-recurrent and mBC. OS was comparable in both arms. Toxicities significantly increased with the addition of BV to chemotherapy, but fatal reactions were rare in all four trials. The addition of BV to conventional first- or second-line chemotherapy is justified in TN mBC since there is still no standard treatment fot this. 

Satisfaction in HER2 testing among medical oncologists- Aiming for multidisciplinary HER2 testing in the Philippines

INTRODUCTION: A multidisciplinary approach is essential to optimize patient care. In the practice of oncology, surgeons, medical oncologists, and pathologists are essential for the histology-based diagnosis of cancer patients. In breast cancer, hormone receptor and HER2 positivity are both predictive and prognostic, and so testing for these has been strongly recommended for every newly diagnosed breast cancer patient. A unique but meaningful information that can be provided by medical oncologists, as customers, is their satisfaction to the services (e.g. HER2 testing) and product (e.g. reports) of the pathology laboratory. Any quality initiative effort to improve HER2 testing can also be extended to hormone receptor (ER/PR) testing. This study measures the general satisfaction of medical oncologists practicing in Metro Manila with local HER2 testing services and reports.METHODS: This cross-sectional study had survey questionnaires distributed to medical oncologists practicing in Metro Manila chosen on the basis of their considerable experience with requesting HER2tests and with the use of anti-HER2 therapy in their management of breast carcinoma patients. Demographics, practice information, rating of satisfaction per laboratory service category, and a checklist of elements of IHC/FISH reports were collected.RESULTS: 32 medical oncologists participated in the survey, most of whom were from tertiary hospitals. Breast carcinoma cases make up around 26-50% of cancer cases in their practice. More than half request HER2 testing for their breast cancer patients. Medical oncologists are generally satisfied with the services for IHC and FISH HER2 testing (composite scores >2) provided by the laboratories. Overall, medical oncologists were very satisfied with diagnostic accuracy and completeness of relevant information in the report. Laboratory services were mostly rated good, with the exception of pathologists' responsiveness to problems and notification of equivocal results. For both IHC and FISH, patient/physician identification, date of service, specimen identification/ site/ type, results, and interpretation were reported to be included in the reports. However, time to/duration of/ type of fixation, method and image analysis method, antibody clone/ vendor, and comment that an FDA-approved method was used, were reported missing by the many.CONCLUSION: For both IHC and FISH, overall satisfaction was found to be moderately directly correlated with diagnostic accuracy. In a country like the Philippines where quality initiatives of laboratories may still be far from ideal, medical oncologists can demand inclusion of their preferences into assessments processes by laboratories and correct assumptions of laboratory managers as to what element of the services and products they value most. Measurement of customer satisfaction can be integrated into the quality assurance programs of laboratories and corresponding hospitals.  

Correlation between demographic, socio-economic, and cancer-specific factors with quality of life scores among newly-diagnosed cancer patients of the Medical Oncology Clinics of the Philippine General Hospital Cancer Institute

INTRODUCTION: Over the last two decades, psychosocial research has explored the experience of cancer patients. This study evaluated if demographic, socio-economic and cancer-specific factors impact and correlate with quality of life (QoL) scores at the time of first consult of newly-diagnosed cancer patients seen at medical oncology clinics of the University of the Philippines¬Philippine General Hospital (UP-PGH) Cancer Institute from 2012-2013.METHODS: Review of charts and interview with a pre-approved and validated questionnaire were done after informed consent. Age, gender, marital status, number of close friends, household income band, employment status, cancer site and stage were recorded. Outcomes were cancer-specific QoL EORTC QLQ-C30 questionnaire and generic QoL EQ5D questionnaire. Scores were correlated with demographic, socio-economic, and cancer¬specific factors.RESULTS: 535 patients were included, 257 male and 278 female. Mean age was 52 years (SD 13.5 years; range20-92 years). Majority (28.7%) belonged to income bracket P4,293-P8,583/month. Majority were married (74.31%) and unemployed (58.4%). Top 5 cancers were colorectal (28.09%), breast (20.70%), head and neck (16.63%), lung (9.97%), lymphoma (7.94%). According to EORTC QLQ-C30, physical functioning (p=0.0037) and cognitive functioning (p=0.003) were significantly correlated with younger patients while role functioning (p=0.04) and emotional functioning (p=0.03) showed negative correlation with older patients. Fatigue was less in female patients (p=0.0005) while being the household head (p=0.0005) was significantly correlated with increased fatigue. According to EQ5D, single patients (p=0.016) had better mobility than the rest of patients. Having 5  family members significantly reported less pain (p=0.038). Breast cancer patients had best QOL while bladder cancer patients had the worst QOL. As cancer stage increased, QOL decreased.CONCLUSION: This is a first baseline study on self-reported QOL among newly-diagnosed Filipino cancer patients, an important relevant reference in the field of psychosocial issues among low-resourced cancer patients in the Philippines.

Immunohistochemical profile, pattern of recurrence, and time to progression of non-metastatic breast cancer patients of the Department of Health-Breast Cancer Medicines Access Program

BACKGROUND: Breast cancer remains to be the leading cause of malignancy among women and survival rates vary worldwide. Molecular and immunohistochemical (NC) profiling of breast cancer has emerged to improve treatment, which led to 6 different breast cancer subtypes luminal-A, luminal-B, Her-2 enriched, basal-like, daudin low, and normal breast. Essentially, this guides clinicians as to the choice of treatment and prognostication of disease. This study evaluates the characteristics of the different IHC subtypes of breast cancer among Filipinos as to pattern of recurrence and time to progression (TIP) within their 1st 2 years of follow-up.METHODS: This is a retrospective cohort study, approved by the University of the Philippines Manila Research Ethics Board (UPMREB). Study population included breast cancer patients enrolled in the DOH-BCMAP and managed at the medical oncology clinics of the Philippine General Hospital (PGH) and Jose R. Reyes Memorial Medical Center (JRRMMC) from 1 May 2011 to 31 December 2013. Patients' demographics, disease and treatment profile were gathered from the medical charts. Patients were grouped into 12 different IHC subtypes utilizing only IHC staining results of Her2neu, ER and PR. Disease progression/ relapse and time to progression (UP) were primary outcomes analyzed and compared between subtypes using SPSS.RESULTS: There were 368 eligible patients; 50% were >50 years old, 48% postmenopausal, 34% stage IIA, and 94% had invasive ductal carcinoma. About 88% completed their chemotherapy regimen, mostly AC-T. At 1 to 2 years follow-up, 18% had disease progression, mostly distant metastasis, with HER2neu(-)/ER(-)/PR(-), HER2(+), and HER2neu(-)/ER(+)/PR(+) subtypes having the most number of disease progression. The HER2neu(-)/ER(-)/PR(-) subtype had the shortest median TTP (11 months 9sd). HER2(+) subtype had median TTP of 14±8 sd, while HER2neu(-)/ER(+)/PR(+) had median TTP at 11.6±7.41 sd. The median TTPs among the different IHC subtypes were statistically comparable. CONCLUSION: Filipinas with non-metastatic breast cancer after surgery and mainly on adjuvant chemotherapy started to develop disease progression/ relapse within the first 2 years of follow-up; 82% had no relapse. At these early years of follow-up, the median TTPs among the different breast cancer IHC subtypes who went into relapse were comparable, although HER2neu(+) regardless of ER/PR subtype tended to have more disease progression, followed by HER2neu(-)/ ER(-)/ regardless of PR subtype, and then HER2neu(-)/ ER(+)/ regardless of PR subtype. IHC resultant HER2neu(+) regardless of ER/PR and HER2neu(-)/ER(-)/PR(-/+) subtypes can serve as early prognosticators of breast cancer relapse.  

Impact of histopathological profile on disease progression of breast cancer patients during the 1st 1-2 years follow-up: Evidence from the Philippine DOH-Breast Cancer Medicine Access Program

INTRODUCTION: Current international consensus confirms that certain histopathologic factors such as tumor morphology, histologic grade and presence of lymphovascular invasion are correlated with prognosis. This retrospective cohort study evaluated the correlation between histopathologic profile and time to disease progression (UP) within the first 1-2 years follow-up of Filipino Stage I-Ill early breast cancer patients.METHODS: This is a retrospective cohort study which included breast cancer patients enrolled in the Department of Health¬Breast Cancer Medicine Access Program (DOH-BCMAP) at the medical oncology clinics of two tertiary hospitals in Manila. Clinical and histopathologic factors were gathered from patient records, and the patients were grouped according to the modified St. Gallen definition of risk categories for patients with breast cancer. Kaplan-Meier survival analysis determined the average UP as well as progression-free survival (PFS). Multivariate logistic regression determined factors contributing to disease progression.RESULTS AND CONCLUSION: Of the 326 patients enrolled in this study, 18% showed progression, with a median HP of 14 months. UP was comparable among the low-, intermediate- and high-risk groups. PFS during the 1st 1-2 years follow-up was estimated to be at 78% for the high-risk group, 83% for the intermediate-risk group, and 86% for the low-risk group. During this 1st 1-2 years follow-up, no studied factors of interest were shown to be significantly correlated with outcome among this predominantly intermediate to high risk for recurrence breast cancer patients. Follow-up of this patients up to 5 or more years would define sustained gains from the DOH-BCMAP.

The effect of DOH-PCSI patient navigation access program for breast cancer on quality of care at the Medical Oncology Clinic at the Philippine General Hospital: The 1st 6 months

INTRODUCTION: Cost has become a limiting factor for indigent breast cancer patients at the Philippine General Hospital (PGH). The Department of Health-Philippine Cancer Society Inc (DOH¬PCSI) Access Program for Breast Cancer Medicine provided free chemotherapy through a patient navigation system in PGH starting January 2012 to improve breast cancer treatment quality. This study looked into the differences of quality care in the non-metastatic setting among enrolled patients in the first 6 months compared to patients outside of the program from 2011-2012.METHODS: This retrospective cohort used follow-up rates and 19 quality care indicators linked to improved outcomes to look into quality of care among patients who were enrolled (n=58) and those who were not (n=118 for 2011 and 2012). Subgroup analyses compared patients in the program and those who were not included in the same period (n=28). Another analysis compared 2011 patients (n= 90) with those in 2012 (n=86). Z¬test for the difference of proportions was done.RESULTS: Attrition rate decreased from 62% in 2011 to 18% in 2012 (pConclusion. The DOH-PCSI Access Program for Breast Cancer Medicine program improved care among breast cancer patients in PGH, noted as early as within its first six months.

Understanding current attitudes in HER2 testing for breast cancer at tertiary referral hospitals of Metro Manila, Philippines

INTRODUCTION: The difficulty of obtaining accurate and reproducible assessment of HER2 status in the Philippines, despite the predictive value of the test for HER2 positive breast cancer patients, may be sufficiently addressed if an effective multidisciplinary approach to HER2 testing is carried out. This may be accomplished by identifying disparities and similarities in HER2 testing for breast cancer.METHODS: This is a cross-sectional study which included medical oncologists who had used trastuzumab for HER2-positive patients. Surgeons, who belonged to the same tertiary hospital as the medical oncologists were also interviewed. The survey questionnaires were administered via face-to-face, mail, or fax. Responses were kept confidential. Questionnaire responses were analysed using summary statistics.RESULTS: There were 35 medical oncologists and 37 surgeons - 93% stated that all women diagnosed with breast cancer should be tested for HER2 at the point of diagnosis; 61% stated that the greatest barrier to initiating HER2 testing was inadequate patient funds. 57% medical oncologists and 65% surgeons believed that HER2 testing for all breast cancer patients at the point of clinical diagnosis was being observed at their hospital. 69% stated that medical oncologists or surgeons should request for HER2 test whoever saw the patients first; 59% stated that whoever saw the patient first provide the patient information about HER2 testing whereas 28% stated it is the medical oncologist who should provide information about HER2 testing. 47% medical oncologist and 63% surgeons stated that surgeons should arrange for breast tissue sample collection; 27% medical oncologists and 20% surgeons stated that pathologists should do this.CONCLUSION: Medical oncologists and surgeons were similar in the opinion that all women diagnosed with breast cancer should be tested for HER2 at the point of diagnosis, financial capability was the greatest barrier for initiating HER2 testing, and whoever saw the patient first should provide patient education. There was disparity on who should request and who should arrange for tissue collection.

Chromosomal aberrations among Filipino health workers at the chemotherapy oncology wards/clinics of a tertiary government hospital

INTRODUCTION: Chromosomal mutations are casual events in neoplasia development. Biomarker cytogenetic assays can determine exposure to mutagenic agents in occupational settings. This study assessed early biological marker chromosomal aberrations among health workers in the chemotheraphy oncology wards/ clinics, exploring its association to the subjects' occupational, environmental and baseline profile.METHODS: This was an IRB approved cross-sectional exploratory study among hospital personnel working in the chemotherapy oncology facility of a tertiary government hospital, who underwent structured interview and blood extraction for cytogenetic assay after informed consent. Study funds only permitted assay of 44 specimens of 144 planned sample size, hence, Stata 6.0 only analyzed data from 44 subjects.RESULTS: All 44 subjects had varying exposure to chemotherapy drug infusions. Of these, 79% had 1.0 breaks per cell (hypersensitive). Predominantly chromatid breaks (CTB), chromatid gaps (CTG), sister chromatid exhanges (SCE) were seen. No significant association was shown between mutagenic sensitivity and baseline characteristics, but with small sample size.CONCLUSION: 21% borderline to hypersensitive mutagenic sensitivity among oncology workers at the tertiary government hospital is relatively significant, despite small sample size, connoting a must preventive promotive practice of chemotherapy administration in the workplace.

Genetic polymorphisms in CYP1A1, GSTM1, GSTP1, GSTT1, NAT1 and NAT2 and oral cavity cancer risk among Filipinos

Polymorphisms in metabolic genes have been shown to modulate susceptibility to oral cavity cancer. Cases (n=176) and controls (n=317) from the Filipino population were genotyped for selected polymorphisms in CYP1A1, GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subjects. The CYP1A1m1/m1 genotype is protective against oral cancer, while being homozygous for the GSTP1 c.313G genotype and heterozygous for the NAT1*10 homozygotes and non-homozygotes for the CYP1A1 m1 allele. The risk from heterozygosity for the NAT1*10 allele was limited to subjects who were not homozygous for the GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental variables, the homozygous GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental risk factors, such as smoking, passive smoking, inverted smoking and tobacco chewing, and environmental protective factors, i.e. moderate consumption of fish sauce (patis) and shrimp paste (bagoong). The GSTP1 c.313G polymorphism increases susceptibility for oral cavity cancer in the Filipino population.

Epidemiological risk factors for cancers of the lung, breast, colon-rectum and oral cavity: A case-control study in the Philippines

INTRODUCTION: In the Philippines, lung, breast, colon-rectum, and oral cavity cancers are among the top 10 most common cancers. This study evaluates the risk factors for these cancers among Filipinos. METHODS: This age-matched case-control study included incident primary cancers (histologically-diagnosed) of the lung, breast (also matched for sex), colon-rectum and oral cavity. Controls (clinically free and no history of cancer) were obtained from the same tertiary hospitals as the cases. Target sample size was 283 cases and 283 controls per cancer type. Conditional logistic regression was done. RESULTS: Exposure to cigarette/tobacco was a significant risk factor for lung (OR of current smoker compared to non-smoker [95% Confidence Interval]: 3.6 [1.6-7.9]) and oral cavity cancers (2.0 [1.2-3.3]); family history (1st degree) for lung (4.3 [1.314.2]) and breast cancers (3.0 [1.2-7.5]); every year increase in age at first pregnancy for breast cancer (1.06 [1.02-1.11]). Other risk factors for oral cavity were passive smoking (2.8 [1.6-5.1]), chewing tobacco (5.2[1.4-19.5]) and inverted cigarette smoking (3.2[1.3-8.1]). Fish sauce (patis) was found to be a protective factor for breast cancer (0.34 [0.22-0.51]) and oral cavity (0.44 [0.25-0.78]) and use of shrimp paste (bagoong) (0.48 [0.27-0.84]) for oral cavity. CONCLUSION AND RECOMMENDATIONS: Except for family history of cancer, the identified risk factors for lung, colon-rectum, and oral cavity cancers are preventable. Proper diet and lifestyle, avoidance of cigarettes and tobacco, and environmental safety in the workplace are key cancer prevention measures. Public awareness campaign and continuing healthcare provider education must always be part of a cancer prevention program.