Faculty of Medicine and Surgery

To ascertain the impact of therapy on gonadal function and reproductive outcome among children treated for Hodgkin's disease, we reviewed the experience at Stanford University Medical Center during the years 19651986. There were 240 children 15 years of age or younger, 92 girls and 148 boys; with median follow-up of 9 years, maximum follow-up was 26 years. Of this cohort, data on gonadal function were available on 20 boys, 5 of whom were considered prepubescent; they had no clinical evidence of sexual maturation and were less than 13 years of age. Evaluation of the boys included testicular biopsy, semen analyses, and the ability to procreate. Serum gonadotropin hormone levels (FSH, LH) were studied in 11 boys who also had semen analyses. Sexual maturation was attained in all boys without the need for androgen replacement. Among the eight boys treated with radiation alone, four were able to father a child (3 following 40-45 Gy pelvic radiation dose, 1 without pelvic radiation) from 3-19 years following treatment. Three others who received 30-44 Gy pelvic radiation were oligospermic when tested at 10 to 15 years post-treatment. Semen analyses in 10 of 12 (83%) boys who had been treated with six cycles of MOPP with or without pelvic radiation revealed absolute azoospermia with no evidence of recovery as along as 11 years of follow-up. Following prolonged azoospermia, 2 of the 12 boys (17%) had recovery of fertility, with normalization of sperm count and/or ability to procreate at 12 and 15 years following treatment. There was no correlation with serum gonadotropin levels and sterility. Data on menstrual history, pregnancy and offspring were available in 86 (92%) of the girls. Seventy-five of the 86 girls (87%) have normal menstrual function. However, none of the females who underwent pelvic radiation without prior oophoropexy has maintained ovarian function. Both the prepubescent and postpubescent boys were affected by 6 cycles of MOPP whether or not pelvic radiation was administered. On the other hand, in girls similarly treated, ovarian injury was directly related to both the number of cycles of chemotherapy and the ovarian radiation dose. The chances of maintaining gonadal function following combined modality treatment are significantly greater among girls than boys. The progeny of patients treated for Hodgkin's disease appear normal and no excess fetal wastage has been noted.

Purpose: The aim of this case report is to present a case of orbital mesenchymal chondrosarcoma sarcoma with multiple recurrences, and to report technical details of a contemporary approach for orbital brachytherapy that can be used in low-resource settings. Material and methods: A 46-year-old female diagnosed with recurrent orbital mesenchymal chondrosarcoma of the left orbit presented with her third local recurrence. The patient proceeded with conservative surgery with planned adjuvant high-dose-rate brachytherapy 2 weeks post-surgery. Brachytherapy mold applicator was fabricated using thermoplastic mask, ProGuide catheter needles, catheter fixation buttons, and a strip of gauze. Ideal catheter placement was done with CT simulation planning. Results: High-risk clinical target volume (HR-CTV) corresponded to gross tumor residual, and intermediate-risk clinical target volume (IR-CTV) corresponded to the whole orbit. Flexitron iridium-192 high-dose-rate (HDR) brachytherapy plan was generated using Oncentra brachytherapy planning system. The treatment plan had HR-CTV total dose of 55.6 Gy and equivalent dose in 2 Gray fractions (EQD 2) of 96 Gy. IR-CTV total dose was 45.5 Gy and EQD 2 of 70 Gy. The plan was evaluated using dose-volume histogram and dosimetric parameters, which showed adequate irradiation of tumor volume and at-risk areas. The patient underwent orbital brachytherapy without any adverse events, except for mild skin erythema. One-year post-treatment showed no local recurrence and no soft tissue necrosis or swelling. Conclusions: In the previously irradiated orbital sarcoma patient, adjuvant brachytherapy is an effective and safe modality for the delivery of sufficient radiation dose to the target, as presented in the current case report. The materials used in the brachytherapy applicator are easily available in majority of radiation therapy centers and can be manufactured even in low-resource settings.

The prevalence and incidence of breast cancer has been increasing worldwide. It has been reported that the Philippines has the highest number of cases in Asia, and breast cancer is now the leading cause of death in the country. This study protocol presents the methodological plan for a quality improvement study that will assess the current practice of breast cancer examination, diagnosis, and management at one of the leading cancer institutions in the Philippines,

Background: The Internet-based Computerized Patient Assessment System (iComPAsS), a remote painand symptom-reporting application was developed to optimize pain monitoring and management. This subanalysis sought to examine factors influencing compliance, to gauge the sustainability of its effects and to guide further development and implementation as part of usual care. Methods: Patients ≥18 years old, with cancer and moderate-severe pain were randomized to standard pain management with pain diary or iComPAsS. Pain and symptom severity (using Edmonton Symptom Assessment Scale) and compliance (to iComPAsS or diary) were evaluated at week 0, 3, 6, 12 and 20. The Treatment Self-regulation Questionnaire (TSRQ), used to assess patient motivation, was administered at week 0, 6, 12 and 20. Pain levels and compliance were compared between the groups using Student's t-test. The Pearson Correlation Coefficient was used to examine the relationship between compliance and pain control, perceived competence in pain self-care, and Relative Autonomy Index (RAI). Results: Out of 100 patients enrolled, 76 were included in the analysis (control; 37; iComPAsS, 39). Baseline pain levels and TSRQ characteristics were similar between the groups. Initial compliance and pain control at week 3 were significantly higher in the iComPAsS group. For the iCompAsS group, compliance directly correlated with uncontrolled pain and intrinsic motivation, and was more sustained compared to the control group. Conclusions: The iComPAsS elicited rapid uptake and sustained compliance through intrinsic motivation. When adopting the iComPAsS for clinical use, patient baseline motivation levels may be assessed using the TSRQ, and depressive symptoms and other barriers to engagement must be identified.

Background: Data on the attitude and perception of adult Filipino cancer patients towards health-related information and communications technology (ICT) and prevalence of access to, willingness to use of and actual usage of ICTs are lacking. We sought to assess the needs, acceptance and readiness of our cancer patient population for a web-based patient-reported outcomes capture system (WPROCS), eventually to be called Internet-based Computerized Patient Assessment System (iComPAssS) in order to guide us in its development. Methods: We conducted a cross-sectional survey among adult cancer patients consecutively seen at our institute, using previously developed questionnaires [WPROCS-Needs, Acceptance and Readiness Assessment (NARA) Questionnaires]. The influence of socio-demographic variables and computer and internet access and usage on attitude and perception towards health-related ICT, willingness to acquire materials, undergo training for its use, and to actually use it was examined using multiple regression analysis. Results: The majority of our respondents (n=130; median age 44, range 28-80) were aged less than 60 (90%), females (78%) and with secondary schooling (98%). The majority (81%) reported good health but 74% reported significant health needs; 85% reported easy access to health care or advice but only 38% reported prompt delivery of health care or advice. The majority (≥95%) have a positive attitude and perception of the idea, and about 90% were willing to acquire materials or undergo training. The only socio-demographic variable that was predictive of acceptance of ICT, willingness to acquire materials, undergo training for its use, and actually use it was younger age. Higher education and income were associated with acceptance of ICT. Frequency of computer/internet use, previous training, and possession of mobile devices to access internet were predictive of acceptance and willingness to acquire materials for ICT use. Internet use for civic and political information and professional life were associated with willingness to acquire materials while internet use in communicating with relatives were associated with willingness to learn ICT usage and to actually use it. Conclusions: Overall, our findings support an opportunity for improving monitoring patient-reported outcomes (PROs) through ICT in our setting.

Background: Telehealth applications may improve health outcomes by engaging patients as active participants, focusing clinic visits on important problems and intensifying symptom management in response to patient reports. Our group developed an internet-based computerized system for patient self-report of symptoms (iComPAsS), and our aim is to evaluate the usability of this mobile application for reporting cancer symptoms among patient and physician end-users. Methods: The literature was surveyed for validated symptom tools available in both English and Filipino. A focused-group discussion (two oncologists, two pain specialists and an international symptom researcher) was conducted to assess face validity and elect an instrument. Application interface and system design was developed collaboratively with information technology consultants over several iterations until beta testing revealed a satisfactory design. Twenty end-users (10 physicians, 10 patients) were invited to assess the app's functionality after a training workshop. App assessment was done using the Mobile Application Rating Scale (MARS). Results: The Edmonton Symptom Assessment System (ESAS) was elected due to its validity, ease of administration and prevalent use in local research and clinical settings. The iComPAsS was shown to be satisfactorily functional on beta testing. It allows patients to report symptom severity, indicate pain location on a body diagram, view prescriptions, and receive notifications from their physicians. On usability testing, engagement, functionality, aesthetics and information scores revealed high and moderate acceptability among physician and patient users, respectively. A clinical trial will be conducted to determine its impact and define maintenance and scale-up issues. Conclusions: The iComPAsS mobile application for patient self-reporting of cancer symptoms is useable and acceptable by both physician and patient end-users.

Background: A web-based patient-reported outcomes capture system (WPROCS) can potentially improve efficacy of symptom monitoring and management and overcome barriers to long-term monitoring and care among adult cancer patients. The patients' needs, acceptance and readiness for such a system need to be explored and understood to support and guide its development. We developed an instrument to survey needs, acceptance and readiness for WPROCS among adult cancer patients. Methods: Literature was searched for applicable instruments in English and for relevant studies to guide modification of such existing instruments according to our objectives. Filipino versions were developed. The modified questionnaires were subjected to content validation by experts and pilot-tested to adult cancer patients. Results: Three questionnaires were developed, one for each dimension-needs, acceptance and readiness. The Needs Assessment Questionnaire explored overall and emotional health; healthcare needs; distressing symptoms and medications; feeding and nutrition; social support and access to healthcare; and ambulatory capacity and functional disability. The Acceptance Assessment Questionnaire explored socio-demographic variables; attitude towards WPROCS, perceived logistic capacity and competency to use it, and willingness to acquire materials, equipment, knowledge and/or access to it when lacking. The Readiness Assessment Questionnaire explored computer and Internet access and use; and computer and Internet skills training and perceived competence. The final instrument, Web-Based Patient-Reported Outcomes Capture System-Needs, Acceptance and Readiness Assessment (WPROCS-NARA), was shown to be practicable, valid and reliable. Conclusions: The WPROCS-NARA is a useful tool in understanding the needs, acceptance and readiness among adult cancer patients for a web-based PROs capture system. We have undertaken a survey using this instrument to guide and support future development of a web-and/or short message service (SMS)-based application to facilitate symptom screening and evaluation of symptom management outcomes through remote symptom-reporting. The findings of this survey are reported elsewhere.

Genes that encode xenobiotic metabolizing enzymes (XMEs) are being reviewed continuously due to their essential functions in the detoxification of toxic compounds implicated in carcinogenesis (López-Cimam et al., 2012). The reactions catalyzed by these enzymes are classified into phase I and phase II reactions. Phase I system utilizes enzymes that initiate the detoxification process by transforming lipid-soluble substances into water-soluble compounds through the introduction of polar and reactive groups into the incoming substrate

The most biologically perilous types of DNA damage are called the double strand breaks (DSBs). A single unrepaired double strand break is reasonable to induce cell death. These events have been linked with the progress of many types of cancer or other genomic defects (Dexheimer, 2013). The two important mechanisms in DSBs are (1) homologous recombination (HR) and (2) non-homologous end-joining (NHEJ). The two repair

Dysbiosis, defined as an imbalance in the gut microbiota caused by too few beneficial bacteria and an overgrowth of bad bacteria, yeast, and/or parasites, is now being associated with several diseases, including the development of colorectal carcinoma (CRC). In this study, the potential association of Clostridioides difficile (formerly Clostridium difficile) with CRC was investigated. Plasma samples obtained from preoperative histologically confirmed CRC patients (n=39) and their age-and sex-matched clinically healthy controls (n=39) were analyzed for antibodies to toxin B of C. difficile (anti-tcdB) by enzyme-linked immunosorbent assay (ELISA). A significantly greater number (p=0.012) of CRC cases (n=26/39, 66.7%) had anti-tcdB IgG levels above the cutoff value compared with controls (n=12/39, 30.8%). Eight cases (8/39, 20.5%) and none of the controls registered anti-tcdB IgA levels above the cutoff value (p=0.0039). Anti-tcdB IgG and IgA levels were not shown to be significantly associated with tumor grade or tumor stage. Anti-tcdB IgG showed 66.7% sensitivity and 69.2% specificity. For anti-tcdB IgA, sensitivity and specificity were 20.5% and 100%, respectively. The positive predictive values for anti-tcdB IgA and IgG were 100% and 68.4%, respectively. The anti-tcdB IgA and IgG negative predictive values were 55.7% and 67.5%, respectively. The results suggest the potential association of C. difficile with CRC and anti-tcdB levels, particularly the IgA level. Hence, anti-tcdB antibodies can be candidate serologic markers for CRC.

Background: Data on the attitude and perception of adult Filipino cancer patients towards health-related information and communications technology (ICT) and prevalence of access to, willingness to use of and actual usage of ICTs are lacking. We sought to assess the needs, acceptance and readiness of our cancer patient population for a web-based patient-reported outcomes capture system (WPROCS), eventually to be called Internet-based Computerized Patient Assessment System (iComPAssS) in order to guide us in its development. Methods: We conducted a cross-sectional survey among adult cancer patients consecutively seen at our institute, using previously developed questionnaires [WPROCS-Needs, Acceptance and Readiness Assessment (NARA) Questionnaires]. The influence of socio-demographic variables and computer and internet access and usage on attitude and perception towards health-related ICT, willingness to acquire materials, undergo training for its use, and to actually use it was examined using multiple regression analysis. Results: The majority of our respondents (n=130; median age 44, range 28-80) were aged less than 60 (90%), females (78%) and with secondary schooling (98%). The majority (81%) reported good health but 74% reported significant health needs; 85% reported easy access to health care or advice but only 38% reported prompt delivery of health care or advice. The majority (≥95%) have a positive attitude and perception of the idea, and about 90% were willing to acquire materials or undergo training. The only socio-demographic variable that was predictive of acceptance of ICT, willingness to acquire materials, undergo training for its use, and actually use it was younger age. Higher education and income were associated with acceptance of ICT. Frequency of computer/internet use, previous training, and possession of mobile devices to access internet were predictive of acceptance and willingness to acquire materials for ICT use. Internet use for civic and political information and professional life were associated with willingness to acquire materials while internet use in communicating with relatives were associated with willingness to learn ICT usage and to actually use it. Conclusions: Overall, our findings support an opportunity for improving monitoring patient-reported outcomes (PROs) through ICT in our setting.

In nasopharyngeal cancer, brachytherapy is given as boost in primary treatment or as salvage for recurrent or persistent disease. The Rotterdam nasopharyngeal applicator (RNA) allows for suboptimal reduction of soft palate radiation dose, based on image-guided brachytherapy plans. Building on the RNA, we propose a novel design, the Benavides nasopharyngeal applicator (BNA). The virtual BNA was reconstructed on two cases (one T1, one T2) previously treated with intracavitary brachytherapy using the RNA. Dose was prescribed to the high-risk clinical target volumes (CTVs) and optimization was such that high-risk CTV D90 ≥ 100% of prescribed dose (PD), intermediate-risk-CTV D90 ≥ 75% PD, and soft palate D2cc ≤ 120% PD. The optimized RNA and BNA image-guided brachytherapy plans were compared in terms of CTV coverage and organs-at-risk sparing. Optimization objectives were more easily met with the BNA. For the T1 case, all three planning objectives were easily achieved in both the RNA and...

Introduction The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiotherapy (CRT). External beam radiotherapy (EBRT) and brachytherapy (BRT) advances in the last decade have resulted in improved local control and survival. There is a lack of data on quality of life (QoL) among survivors. Objective This systematic review aimed to synthesize published data on QoL among LACC survivors treated with CRT and determine clinical factors of QoL. Methods Systematic literature search was conducted in PubMed, EBSCO, and ScienceDirect for relevant articles published in 2010 to 2020. Eligible studies on LACC survivors aged 18 years and above, who reported QoL after CRT, were included. Screening and data extraction were done by two pairs of independent reviewers. Results Five cohort studies, three cross sectional studies, and one clinical trial were included. Reported temporal evolution of QoL varied: two studies reported improvement of overall QoL, while four r...

Introduction: The IRESSA Survival Evaluation in Lung Cancer (ISEL) phase III study compared the efficacy of gefitinib (IRESSA) versus placebo in patients with refractory advanced non-small cell lung cancer (NSCLC). Although a statistically significant difference in survival was not seen between gefitinib and placebo in the overall ISEL population, preplanned subset analyses demonstrated a significant survival benefit in patients who had never smoked and in patients of Asian origin. Methods: In ISEL, 1692 patients who were refractory to or intolerant of their latest chemotherapy were randomized to receive either gefitinib (250 mg/day) or placebo, plus best supportive care. Preplanned subgroup analyses included an assessment of patients who were of Asian origin (n ϭ 342). Results: Two hundred thirty-five patients of Asian origin received gefitinib, and 107 received placebo. In these patients, treatment with gefitinib significantly improved survival compared with placebo (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.48, 0.91; p ϭ 0.010; median survival, 9.5 versus 5.5 months). Patients of Asian origin also experienced statistically significant improvements in time to treatment failure with gefitinib compared with placebo (HR, 0.69; 95% CI, 0.52, 0.91; p ϭ 0.0084; 4.4 versus 2.2 months), and objective response rates were higher with gefitinib than with placebo (12 versus 2%). Gefitinib was generally well tolerated in patients of Asian origin, with rash and diarrhea being the most common adverse events. No unexpected adverse events were observed. Conclusions: Treatment with gefitinib was associated with a significant improvement in survival in a subgroup of patients of Asian origin with previously treated refractory advanced NSCLC.

Background: The World Health Organization recognizes depression as one of the most burdensome diseases in the world. Among cancer patients, depression is significantly associated with shorter survival, independent of the influence of biomedical prognostic factors. Although cancer is the third leading cause of morbidity and mortality among Filipinos, little is known about depressive symptoms and their influence on health-related quality of life in this population. We assessed the prevalence of, and factors associated with, depressive symptoms and their influence on health-related quality of life in Filipino patients with cancer. Methods: The Patient Health Questionnaire (PHQ)-8 and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were administered to all inpatients and outpatients, age > = 18 years presenting for cancer treatment. Results: Twenty-two percent (n = 53/247) were categorized as depressed, using a PHQ-8 cutoff of ‡ 10. Depressed patients scored lower on cognitive, emotional, role, physical, and social functioning than those who scored PHQ < 10 (all P < 0.001). Depression varied by disease status, performance status and marital status (all P < 0.001). However, only performance status (OR [odds ratio] = 2.20; 95% CI = 1.60, 3.00) and disease status (OR = 2.4; 95% CI = 1.13, 5.22) were significantly associated with depression in the multivariable model. Conclusions: Depression is prevalent in Filipino cancer patients. The findings provide empirical support for the development of mental health services in this understudied population. This study, the first to assess the prevalence of and factors associated with depression in Filipino cancer patients, needs further validation.

BACKGROUND: The role of certain gut microbes in the development of colorectal cancer has recently been understood. In our previous work, we have reported the reactivity of serum collected from CRC patients to peptide mimotopes of bacterial antigens associated with the development of CRC, hence, their potential in its detection. Here, we evaluate the diagnostic parameters of an anti-Clostridioides difficile toxin B (tcdB) peptide mimotope IgG and IgA antibody-capture enzyme-linked immunosorbent assay (ELISA) in the detection of CRC. METHODS: Prediction of the immunogenic epitopes of tcdB was made using the in silico B-cell epitope mapping tools available at the Immune Epitope Database and Analysis Resources (IEDB). Synthetic peptide analogs of the predicted epitopes which were used in the immunoassays were synthesized and purchased from Genscript (New Jersey, USA). Presence of anti-peptide IgG and IgA from serum collected from patients diagnosed with colorectal cancer were detected by a peptide antibody-capture indirect ELISA protocol developed in this study. Diagnostic parameters were computed. RESULTS: The amino acid position 1465 to 1474 of the reported sequence of tcdB (PDB Accession No. AGG91641.1) was predicted to be immunogenic. The peptide antibody-capture ELISA developed in this study gave diagnostic specificities of 94.9% and 97.4%, positive predictive values (PPV) of 86.6% and 93.3%, and likelihood ratios of 6.5 and 14.0 for IgG and IgA, respectively. Our results show the potential of the immunoassay designed in ruling in possibility of CRC during diagnosis.

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The RAD51 gene encodes the protein that plays a central role in the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway. Association of RAD51 single nucleotide genetic polymorphism (SNP) with the development of cancer has been observed to be tumor site- and race-specific. Thus, this study aimed to determine the potential association between RAD51 135G&gt;C SNP and breast cancer among selected Filipinos. Patients with histologically confirmed breast cancer (n = 60) seen at the University of Santo Tomas Hospital (USTH Manila) were age- and sex-matched with clinically healthy controls (n = 60). Genomic DNA was extracted from the blood of participants and analyzed for RAD51 genotype by polymerase chain reaction – restriction enzyme fragment length polymorphism (PCR-RFLP). A significantly higher incidence of RAD51 C/C genotype was seen among the cases than the controls (p &lt; 0.05). The more common G/C genotype was not associated with breast cancer dev...