Teleconsultation Perceptions of Medical and Radiation Oncologists in the COVID-19 and Post-COVID-19 Era: A National Survey in the Philippines.

PURPOSE: The study reports on the current perception of medical and radiation oncologists regarding teleconsultation in the Philippines. Before the COVID-19 pandemic, the adoption of telemedicine was not widespread. With movement restrictions imposed during the pandemic, physicians were compelled to use telemedicine. It is uncertain whether physicians will still adopt its use in practice in the post-COVID-19 era. This study gives insight into the possible adaptation of this mode of consultation in the future, especially in areas with limited health care resources. MATERIALS AND METHODS: We conducted a national survey among medical oncologists and radiation oncologists in the Philippines. A 43-item online survey was developed, validated, and administered to the oncologists. The demographics and data from categorical questions were reported as frequencies and percentages. RESULTS: A total of 142 responses were gathered from 82 medical oncologists and 60 radiation oncologists. There was agreement among participants that, during the pandemic, teleconsultation could be used for the first visit, diagnostic workup request, treatment explanation, follow-up care, and chronic disease management. There was disagreement whether cancer diagnosis disclosure and cancer prognosis revelation could be performed via teleconsultation, and there was agreement that emergency consultation and physical examination would warrant a face-to-face consultation. After the COVID-19 pandemic, 78.7% intend to continue using teleconsultation except for emergency consultations, first visits, physical examination, diagnosis disclosure, and cancer prognosis revelation. CONCLUSION: Teleconsultation was perceived by oncologists as an acceptable method of providing cancer care during and after the COVID-19 pandemic. Oncologists also intend to use teleconsultation in the post-COVID-19 era in certain aspects of patient care.

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma.

PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.

Outcomes with definitive radiotherapy among patients with locally advanced cervical cancer with relative or absolute contraindications to cisplatin: A systematic review and meta-analysis.

BACKGROUND: The standard treatment for locally advanced cervical cancer (LACC) is chemoradiation (CRT) with cisplatin, followed by brachytherapy, but is less defined for cisplatin-intolerant patients. We synthesized evidence on treatment outcomes with definitive radiotherapy (RT) with or without chemotherapy (ChT) in these patients. METHODS: We performed a systematic search and included 20 relevant studies. We extracted data on response, survival, compliance, and toxicity, and performed meta-analyses of outcome rates and risk ratios. Sensitivity and subgroup analyses were performed to explore sources of heterogeneity. Meta-regression was performed to examine the effects of other variables. RESULTS: Due to lack of comparative data, most comparisons were indirect and derived from the proportional meta-analyses. Complete response (85%) and survival (62% 5yOS) rates are comparable to those published for LACC without contraindications to cisplatin. Survival rate is better with CRT than RT alone (5yOS, 73% vs 58%), and with nodal boost (NB) than without (5yOS, 71% vs 56%). Carboplatin CRT is associated with lower 5yOS (44%) but better ChT compliance (86%) when compared to other interventions. ChT compliance is better in renal failure than elderly cohorts (89% vs 67%). RT compliance is lower with CRT than RT alone (90% vs 96%), and higher with NB than none (96% vs 93%). NB is associated with lower RT compliance than no NB, when ChT is given. Meta-regression results affirm ChT and NB to be significant positive factors for survival, and NB, which is associated with greater use of advanced RT techniques, for RT compliance. CONCLUSION: For those with relative contraindications, cisplatin CRT is effective and well-tolerated. For those with absolute contraindications, carboplatin is well-tolerated but with unclear effectiveness. Nodal boost is effective and well-tolerated, but is less tolerated when concurrent ChT is given.

Phase 1/2 trial evaluating the effectiveness and safety of dose-adapted Hypofractionated pelvic radiotherapy for Advanced Cervical cancers INeligible for ChemoTherapy (HYACINCT).

BACKGROUND: The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiation (CRT) followed by brachytherapy (BRT). The addition of chemotherapy (ChT) to radiotherapy (RT) is associated with a 7.5% improvement in overall survival but with more grade 3-4 acute toxicities (16.4% vs 4.9%, CRT vs RT alone). The risk-benefit ratio could be less favorable in advanced disease with renal dysfunction secondary to tumor-related hydronephrosis; borderline cardiac function; and frail patients. RT alone followed by BRT achieves long-term locoregional control <62%. Hypofractionated RT (HF-RT) using older techniques result in comparable disease control and low late toxicity rates (4-8%). Dose-adapted HF-RT using intensity-modulated RT with nodal simultaneous integrated boost (nSIB) could improve tumor control and toxicity, when ChT is contraindicated. METHODS: The HYACINCT study is a two-phase study to determine the effectiveness and safety of HF-RT with nSIB in LACC when ChT is contraindicated. Phase 1 is a dose-escalation study using standard 3 + 3 design, to determine the maximum tolerated dose (MTD) for nSIB in combination with pelvic HF-RT (2.67 Gy x 15 fractions). Phase 2 is a single-arm clinical trial using Simon's two-stage design, to assess the efficacy of HF-RT with nSIB in terms of tumor response. Adult women with biopsy-proven, untreated LACC, with contraindication to ChT will be included in this trial. DISCUSSION: For the phase 1, the primary endpoint is dose-limiting toxicity (DLT), or any grade ?3 acute or sub-acute toxicity. The dose level at which incidence of DLT is ?33% is defined as the maximum tolerance dose (MTD). For the phase 2, the primary endpoint is complete response at 3 months post-treatment. Secondary outcomes are progression-free and overall survival, acute and late toxicity, and patient-reported outcomes (EPIC, EORTCQLQ C30 + CX24, PGIC, PCIS). Trial registration: NCT05210270.

Assessing the Effect of Radiotherapy in Addition to Surgery in Colon Adenocarcinomas: a Systematic Review and Meta-analysis of Contemporary Evidence.

PURPOSE: This study aims to review the contemporary evidence investigating radiotherapy (RT) in addition to surgery for colon adenocarcinomas. METHODS: We searched the following databases: PubMed, Science Direct, Scopus, ASCOpubs, the Cochrane Library, and Google Scholar. Studies (since January 2005) comparing outcomes of high-risk colon adenocarcinomas who underwent RT in addition to surgery versus no RT were eligible. Pooling of outcomes from published results or from analysis of survival curves was done. Subgroup analysis was conducted to determine if the efficacy of RT varies with RT timing. RESULTS: Eight studies were included (five retrospective cohorts, three population-based studies). Pooled analysis from retrospective cohorts showed a reduction in 5-year LR (OR 0.41; 95% CI 0.21-0.79; p = 0.007) in the RT group. A benefit in 3-year (OR 1.81; 95% CI 1.15-2.87; p = 0.01) and 5-year (OR 2.10; 95% CI 1.21-3.63; p = 0.008) DFS and in 3-year (OR 2.55; 95% CI 1.43-4.54; p = 0.001) and 5-year (OR 2.00; 95% CI 1.17-3.41; p = 0.01) OS was seen in the RT group. The OS benefit was demonstrated in the subgroup analysis of neoadjuvant RT, but not with adjuvant RT. The improvement in OS with neoadjuvant RT was supported by a population-based study from NCDB, while results from two population-based studies investigating adjuvant RT were conflicting. CONCLUSION: Taking into account the limitations of the studies, our review of evidence suggests a possible role of RT in improving oncologic outcomes of select colon adenocarcinomas. Prospective studies are needed to definitively assess the value of RT for colon cancer.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.

XRCC4 c.1394G>T Single Nucleotide Polymorphisms and Breast Cancer Risk among Filipinos

Background: The identification of cancer-associated single nucleotide polymorphisms (SNP) and mutation genes is a promising approach in recognizing individuals who are at risk of developing cancer. Hence, this study was conducted to determine the association between XRCC4 c.1394G>T SNP and breast cancer development among Filipinos. Methods: Genotyping for XRCC4 c.1394G>T SNP was performed on breast cancer patients (n=103) and their age- and sex- matched clinically healthy controls (n=103) by polymerase chain reaction ­ restriction fragment length polymorphism. Results: Significant difference in genotype (p=0.007) and allele (p=0.003) frequencies in XRCC4 c.1394G>T was observed between the breast cancer cases and controls. Carriers of the XRCC4 c.1394 G>T genotype were observed to have significantly higher risk of developing breast cancer compared to individuals with T/T genotype (OR=2.67, 95% CI: 1.36 ­ 5.25). XRCC4 c.1394G>T combined with passive smoking may also significantly increase risk of breast cancer (OR=14.73; 95% CI= 9.88-18.86). Conclusion: XRCC4 c. 1394G>T may be associated with breast cancer development among Filipinos.

GSTM1 and GSTT1 Genetic Polymorphisms and Breast Cancer Risk in Selected Filipino Cases

Background: The association of genetic polymorphisms with cancer development has been shown to be race- and tumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genes are associated with breast cancer among selected Filipinos. Methods: A total of 136 histologically confirmed breast cancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from blood samples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results: The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantly different (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that risk for breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1 positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1 null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion: This study suggests that variants of GSTM1 and GSTT1 may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when these genotypes were combined with lifestyle or environmental factors.

Neoadjuvant Radiotherapy Versus No Radiotherapy for Stage IV Rectal Cancer: a Systematic Review and Meta-analysis.

PURPOSE: The aim of this study is to review the contemporary evidence comparing neoadjuvant radiotherapy (NRT) versus no radiotherapy (no RT) in patients with stage IV rectal cancer. METHODS: Literature was searched for studies using the following databases: Pubmed, EMBASE, Science Direct, Scopus, ASCOpubs, the Cochrane Library, and Google Scholar. Studies reporting outcomes for stage IV rectal cancer patients who underwent NRT or no RT were selected. RESULTS: A total of eight studies were included in this review (one RCT, five retrospective cohorts, two population-based studies). The only RCT in this review reported no significant difference in 2- and 5-year local recurrence (NRT versus no RT) 10.1% versus 23.8%, and 15.9% versus 26.9%, respectively. However, multivariate analysis showed the effect of treatment might not have differed between subgroups according to stage. Pooled analysis from five retrospective studies showed significantly improved local recurrence-free survival (LRFS) with NRT (risk ratio [RR] 1.15; 95% CI 1.01-1.31, p = 0.03), which was maintained in the subgroup who underwent metastasectomy. (RR 1.18; 95% CI 1.01-1.37, p = 0.04). Pooled 5-year overall survival (OS) showed a statistically significant benefit with NRT (RR 1.47; 95% CI 1.14-1.89, p = 0.003), which was not seen in the subgroup who underwent metastasectomy (RR 1.31; 95% CI 0.94-1.82, p = 0.11). CONCLUSION: The current available evidence shows an LRFS benefit with NRT over no RT in patients with stage IV rectal cancer. The review also suggests a possible OS benefit with NRT, although this finding should be interpreted with caution.

A novel applicator design for intracavitary brachytherapy of the nasopharynx: Simulated reconstruction, image-guided adaptive brachytherapy planning, and dosimetry.

PURPOSE: 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). METHODS AND MATERIALS: 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. RESULTS: 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 BNA, but with 18-19% lower soft palate doses with the BNA. For the T2 case, the CTV planning objectives were achieved in both the RNA and BNA, but the soft palate constraint was only achieved with the BNA, with 38-41% lower soft palate doses. CONCLUSIONS: Compared to the RNA, the BNA permits easier optimization and improves therapeutic ratio by a significant reduction of soft palate doses, based on simulation using a proposed system for CTV/organs-at-risk delineation, prescription, and optimization for image-guided adaptive brachytherapy. Clinical piloting using a prototype is necessary to evaluate its feasibility and utility.

Immunogenicity of a Fap2 peptide mimotope of Fusobacterium nucleatum and its potential use in the diagnosis of colorectal cancer.

BACKGROUND: The role of Fusobacterium nucleatum Fap2 protein in the development of colorectal cancer has recently been explained. Fap2, when bound to the human inhibitory receptor, TIGIT, inhibits the cytotoxic activity of natural killer (NK) cells against cancer cells, thus, allowing proliferation of the latter eventually leading to tumor growth. The aim of the study was to identify the immunogenicity of a peptide mimotope of the Fap2 protein and to determine the reactivity of colorectal cancer patients' sera against the mimotope. METHODS: Immunogenic epitope of the Fap2 protein of F. nucleatum was selected using the B-cell epitope prediction of the Immune Epitope Database and Analysis Resource (IEDB). The immunogenicity of the synthetic peptide mimotope of the Fap2 protein was determined in animal models and reactivity of colorectal cancer patients' sera against the mimotope was done by indirect ELISA. RESULTS: Results show that the selected peptide mimotope, with sequence TELAYKHYFGT, of the outer membrane protein Fap2 of F. nucleatum is immunogenic. Increase in the absorbance readings of peptide-immunized rabbit sera was observed starting Week 1 which was sustained up to Week 10 in the indirect ELISA performed. Colorectal cancer cases (n = 37) were all reactive in an ELISA-based analysis using the mimotope as the capture antigen. CONCLUSIONS: In this study, we identified an immunogenic epitope of the Fap2 protein of the Fusobacterium nucleatum. We demonstrated the reactivity of serum of histopathologically confirmed CRC patients in a peptide-capture indirect ELISA which may serve as proof of concept for the development of CRC diagnostics.

Validation of the MD Anderson Symptom Inventory-Head-and-Neck-Filipino (MDASI-HN-F): clinical utility of symptom screening among patients with head-and-neck cancer.

CONTEXT: Symptom burden and quality of life (QOL) are of particular importance in head-and-neck cancer treatment. The MD Anderson Symptom Inventory-Head-and-Neck (MDASI-HN) is a simple symptom assessment tool practicable for patient follow-up, but a validated Filipino translation was previously unavailable. OBJECTIVES: The objectives of this study were to develop a valid Filipino translation of the MDASI-HN, to test the sensitivity of the validated MDASI core-F, and to report the prevalence and pattern of head-and-neck symptoms in our cohort. METHODS: An MDASI-HN-Filipino (MDASI-HN-F) version was developed and examined for convergent validity, internal consistency, test-retest reliability, known-group validity and sensitivity to change. Eligible participants were aged 18-80 years, with histopathologically-proven head-and-neck (except thyroid) cancer, able to understand and read English and Filipino, and without cognitive impairment or other conditions precluding self-administration of the questionnaire. RESULTS: Participants (n=100) were aged 18-76 years; the majority were aged <60, male, married, had college schooling, or were from a Tagalog-speaking region. The validity of the MDASI HN-F was demonstrated in all parameters. Age or educational attainment did not affect convergent validity or test-retest reliability. At baseline, 48% had multiple moderate/severe symptoms and 38% had at least one severe symptom. CONCLUSIONS: The MDASI-HN-F is valid, reliable and sensitive. The sensitivity of the MDASI core-F is demonstrated, and its validity and reliability reaffirmed. Moderate and severe head-and-neck symptoms are prevalent in early-stage and advanced-stage head-and-neck cancers, reflecting the utility of symptom screening for improvement of symptom management, QOL and compliance to treatment.

Depressive symptoms among cancer patients in a Philippine tertiary hospital: prevalence, factors, and influence on health-related quality of life.

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.