Displaying publications 21 - 40 of 50 in total

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  1. Gan GG, Tey KWF, Mat S, Saad M, Bee PC, Abdul Malik R, et al.
    Asian Pac J Cancer Prev, 2022 Nov 01;23(11):3905-3914.
    PMID: 36444604 DOI: 10.31557/APJCP.2022.23.11.3905
    BACKGROUND: Quality of life (QOL) of family caregivers of cancer patients is usually affected due to increase in caregiver burden. Their QOL has not garnered much attention by many including the health professionals and community. This study aims to explore the QOL of family caregivers of cancer patients in a multi-ethnic country in Asia and to investigate its associate factors.

    METHODS: This is a cross-sectional study where family caregivers and patients who were diagnosed of cancers within 12 months were recruited. QOL of caregivers were measured using The Caregiver Quality of Life Index-Cancer (CQOLC). Psychological distress was measured using Hospital anxiety and depressive scale. Logistic regression analysis was performed to determine the related factors of QOL of caregivers.

    RESULTS: A total of 458 patients/caregiver pairs were included. Symptoms of anxiety and depression reported by caregivers were 24.9% and 24.2% respectively. Caregivers of patients with solid tumors have better CQOLC score compared to those who cared for patients with hematological cancers (91.25 vs 86.75). Caregivers of non-Malay ethnicity, those caring for patients with advanced stage cancer and with hematological cancers had significantly poorer QOL. QOL of caregivers are also significantly affected when patients demonstrated anxiety symptoms.

    CONCLUSION: This study provides detailed evaluation of the QOL of caregivers of cancer patients in Malaysia. The significant psychological distress and low caregiver QOL indicate the urgent need for comprehensive supports for caregivers with cancer patients, especially those caring for patients with haematological cancers.

  2. Chai CS, Liam CK, Poh ME, Ong DB, Pang YK, Cheah PL, et al.
    Cancer Manag Res, 2020;12:5439-5450.
    PMID: 32753961 DOI: 10.2147/CMAR.S253760
    BACKGROUND: This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibitor (TKI).

    METHODS: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017.

    RESULTS: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84-6.25, p = 0.104).

    CONCLUSION: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations.

  3. Soon SS, Chia WK, Chan ML, Ho GF, Jian X, Deng YH, et al.
    PLoS One, 2014;9(9):e107866.
    PMID: 25250815 DOI: 10.1371/journal.pone.0107866
    Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older.
  4. Bhoo-Pathy N, Yip CH, Hartman M, Saxena N, Taib NA, Ho GF, et al.
    Eur J Cancer, 2012 May;48(7):982-9.
    PMID: 22366561 DOI: 10.1016/j.ejca.2012.01.034
    Adjuvant! Online is a free web-based tool which predicts 10-year breast cancer outcomes and the efficacy of adjuvant therapy in patients with breast cancer. As its prognostic performance has only been validated in high income Caucasian populations, we validated the model in a middle income Asian setting.
  5. Wong HS, Subramaniam S, Alias Z, Taib NA, Ho GF, Ng CH, et al.
    Medicine (Baltimore), 2015 Feb;94(8):e593.
    PMID: 25715267 DOI: 10.1097/MD.0000000000000593
    Web-based prognostication tools may provide a simple and economically feasible option to aid prognostication and selection of chemotherapy in early breast cancers. We validated PREDICT, a free online breast cancer prognostication and treatment benefit tool, in a resource-limited setting. All 1480 patients who underwent complete surgical treatment for stages I to III breast cancer from 1998 to 2006 were identified from the prospective breast cancer registry of University Malaya Medical Centre, Kuala Lumpur, Malaysia. Calibration was evaluated by comparing the model-predicted overall survival (OS) with patients' actual OS. Model discrimination was tested using receiver-operating characteristic (ROC) analysis. Median age at diagnosis was 50 years. The median tumor size at presentation was 3 cm and 54% of patients had lymph node-negative disease. About 55% of women had estrogen receptor-positive breast cancer. Overall, the model-predicted 5 and 10-year OS was 86.3% and 77.5%, respectively, whereas the observed 5 and 10-year OS was 87.6% (difference: -1.3%) and 74.2% (difference: 3.3%), respectively; P values for goodness-of-fit test were 0.18 and 0.12, respectively. The program was accurate in most subgroups of patients, but significantly overestimated survival in patients aged <40 years, and in those receiving neoadjuvant chemotherapy. PREDICT performed well in terms of discrimination; areas under ROC curve were 0.78 (95% confidence interval [CI]: 0.74-0.81) and 0.73 (95% CI: 0.68-0.78) for 5 and 10-year OS, respectively. Based on its accurate performance in this study, PREDICT may be clinically useful in prognosticating women with breast cancer and personalizing breast cancer treatment in resource-limited settings.
  6. Saad M, Chong FLT, Bustam AZ, Ho GF, Malik RA, Ishak WZW, et al.
    Indian J Cancer, 2019 1 4;55(2):157-161.
    PMID: 30604728 DOI: 10.4103/ijc.IJC_581_17
    BACKGROUND: Scalp cooling has been shown in several studies to be an effective method in preventing chemotherapy-induced alopecia (CIA). Data on the use of scalp cooling in Asian countries are limited, and evidence for its use and efficacy among our patients are not available.

    OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of scalp cooling among breast cancer patients in our study population.

    METHODS: Consecutive breast cancer patients receiving FE75C, FE100C, FE100C-D, docetaxel75 or docetaxel, and cyclophosphamide (TC) at our treatment center were recruited and allocated to the treatment (scalp cooling, DigniCapTM system) or control group in this prospective nonrandomized controlled study. The assessment of alopecia was carried out using the World Health Organization grading system and clinical photographs.

    RESULTS: Seventy patients were recruited, but only 25 completed the study and were evaluable for analysis. Five of 12 patients (42%) in the scalp cooling group managed to preserve hair. Two of three patients who received FE75C and TC regimens had minimal hair loss. All patients treated with FE100C had severe hair loss. Half of all patients who received scalp cooling throughout chemotherapy rated the treatment as reasonably well tolerated. The most common reason for discontinuing scalp cooling was intolerance to its side effects.

    CONCLUSION: Scalp cooling is potentially effective in reducing CIA caused by docetaxel, TC, and FE75C chemotherapy regimen. However, it was not well tolerated by our study population. The dropout rate was high, and this needs to be taken into consideration when pursuing further trials in a similar setting.

  7. Wong LP, Kong YC, Bhoo-Pathy NT, Subramaniam S, Bustamam RS, Taib NA, et al.
    JCO Oncol Pract, 2021 04;17(4):e548-e555.
    PMID: 32986532 DOI: 10.1200/JOP.20.00002
    PURPOSE: The breaking of news of a cancer diagnosis is an important milestone in a patient's cancer journey. We explored the emotional experiences of patients with cancer during the breaking of news of a cancer diagnosis and the arising needs in a multiethnic Asian setting with limited supportive cancer care services.

    METHODS: Twenty focus group discussions were conducted with 102 Asian patients with cancer from diverse sociodemographic backgrounds. Thematic analysis was performed.

    RESULTS: While most participants, especially younger patients with young children, experienced intense emotional distress upon receiving a cancer diagnosis, those with a family history of cancer were relatively calm and resigned. Nonetheless, the prior negative experience with cancer in the family made affected participants with a family history less eager to seek cancer treatment and less hopeful for a cure. Although a majority viewed the presence of family members during the breaking of bad news as important, a minority opted to face it alone to lessen the emotional impact on their family members. Difficulties disclosing the news of a cancer diagnosis to loved ones also emerged as an important need. Sensitive and empathetic patient-physician communication during the breaking of news of a cancer diagnosis was stressed as paramount.

    CONCLUSION: A patient-centered communication approach needs to be developed to reduce the emotional distress to patients and their families after the breaking of bad news of a cancer diagnosis. This is expected to positively affect the patients' subsequent coping skills and attitudes toward cancer, which may improve adherence to cancer therapy.

  8. Rajah HDA, Chan CMH, Kong YC, Wong LP, Bustaman RS, Ho GF, et al.
    Support Care Cancer, 2021 Oct;29(10):5811-5819.
    PMID: 33742239 DOI: 10.1007/s00520-021-06148-2
    INTRODUCTION: Delivery of supportive cancer care is often deemed a low priority in resource-limited settings. We aimed to explore the sources of emotional distress, the related support and the unmet needs of cancer survivors in Malaysia, where cancer survivorship services are presently limited.

    METHOD: Twenty focus group discussions were conducted with 102 cancer patients from diverse ethnic and socioeconomic backgrounds. Thematic analyses were performed.

    RESULTS: Patient narratives suggested that emotional distress arose from direct and indirect stressors. Direct stressors comprised physical and cognitive side effects of cancer surgery and therapies, and fear of recurrence. Indirect stressors included worry over dependent family members, financial distress following cancer, working with cancer and lack of practical support at home. Distress from altered physical appearances, fear of recurrence and lack of practical support were mainly raised by women, implying that men and women may have disproportionate emotional needs. Emotional support largely came from informal sources including self, family, friends and religion. While formal emotional support from professional counsellors and cancer support groups was acknowledged as important, it appeared to be largely lacking. Unmet needs in coping with fear of recurrence, financial distress, workplace discrimination and household chores were particularly highlighted.

    CONCLUSION: The unmet needs revealed in this study provide insights to initiate actionable changes to improve the emotional wellbeing of people living with cancer in settings where cancer survivorship services are still in its infancy.

  9. Chang JW, Guo J, Hung CY, Lu S, Shin SJ, Quek R, et al.
    Asia Pac J Clin Oncol, 2017 12;13(6):423-427.
    PMID: 28198155 DOI: 10.1111/ajco.12670
  10. Fnu N, Kuan WC, Kong YC, Bustamam RS, Wong LP, Subramaniam S, et al.
    Ecancermedicalscience, 2022;16:1449.
    PMID: 36405936 DOI: 10.3332/ecancer.2022.1449
    Background: Evidence on the financial experiences of cancer survivors living in settings with pluralistic health systems remains limited. We explored the out-of-pocket costs, the resulting financial impact and the coping strategies adopted by cancer survivors in Malaysia, a middle-income country with a government-led tax-funded public health sector, and a predominantly for-profit private health sector.

    Methods: Data were derived from 20 focus group discussions that were conducted in five public and private Malaysian hospitals, which included 102 adults with breast, cervical, colorectal or prostate cancers. The discussions were segregated by type of healthcare setting and gender. Thematic analysis was performed.

    Results: Five major themes related to cancer costs emerged: 1) cancer therapies and imaging services, 2) supportive care, 3) complementary therapies, 4) non-medical costs and 5) loss of household income. Narratives on out-of-pocket medical costs varied not only by type of healthcare setting, clinical factors and socioeconomic backgrounds, but also by private health insurance ownership. Non-health costs (e.g. transportation, food) and loss of income were nonetheless recurring themes. Coping mechanisms that were raised included changing of cancer treatment decisions, continuing work despite ill health and seeking financial assistance from third parties. Unmet needs in coping with financial distress were especially glaring among the women.

    Conclusion: The long-term costs of cancer (medications, cancer surveillance, supportive care, complementary medicine) should not be overlooked even in settings where there is access to highly subsidised cancer care. In such settings, patients may also have unmet needs related to non-health costs of cancer and loss of income.

  11. Islam T, Musthaffa S, Hoong SM, Filza J, Jamaris S, Cheng ML, et al.
    Support Care Cancer, 2021 May;29(5):2631-2638.
    PMID: 32968861 DOI: 10.1007/s00520-020-05776-4
    PURPOSE: Wider breast cancer (BC) treatment options, short consultation time with physicians, lack of knowledge, and poor coping skills at the time of diagnosis may affect patients' decisions causing treatment delays and non-adherence. To address this gap, a breast care nurse video orientation program was started. Our aim was to evaluate the video on patients' knowledge, satisfaction, and treatment adherence.

    METHODS: The video was developed using the BC delay explanatory model. A self-administered pre- and post-survey on 241 newly diagnosed BC patients in University Malaya Medical Center was performed. The Wilcoxon matched paired signed rank test was used to evaluate patients' pre and post perceived knowledge using a Likert scale 0 to 4 (0 = "no knowledge," 4 = "a great degree of knowledge"). Treatment adherence among participants were measured after 1-year follow-up.

    RESULTS: Eighty percent of the patients reported that the video met or exceeded their expectations. In total 80.5% reported that the video was very effective and effective in improving their perspective on BC treatments. There was improvement in perceived knowledge for treatment options (mean scores; M = 0.93 versus M = 2.97) (p < 0.001) and also for perceived knowledge on types of operation, information on chemotherapy, radiotherapy, hormone therapy, healthy diet, physical activity after treatments, and care of the arm after operation(p < 0.001). In total 89.4%, 79.3%, and 85.9% adhered to surgical, chemotherapy, and radiotherapy recommended treatment, respectively.

    CONCLUSION: The video improved patients' perceived knowledge and satisfaction. The program improved access not only to new BC patients but also the public and found sustainable using the YouTube platform.

  12. Karajacob AS, Azizan NB, Al-Maleki ARM, Goh JPE, Loke MF, Khor HM, et al.
    PLoS One, 2023;18(4):e0284043.
    PMID: 37068057 DOI: 10.1371/journal.pone.0284043
    Overgrowth of Candida yeasts in the oral cavity may result in the development of oral thrush in immunocompromised individuals. This study analyzed the diversity and richness of the oral mycobiota of patients clinically diagnosed with oral thrush (OT), follow-up of oral thrush patients after antifungal therapy (AT), and healthy controls (HC). Oral rinse and oral swab samples were collected from 38 OT patients, 21 AT patients, and 41 healthy individuals (HC). Pellet from the oral rinse and oral swab were used for the isolation of oral Candida yeasts on Brilliance Candida Agar followed by molecular speciation. ITS1 amplicon sequencing using Illumina MiSeq was performed on DNA extracted from the oral rinse pellet of 16 OT, 7 AT, and 7 HC oral rinse samples. Trimmed sequence data were taxonomically grouped and analyzed using the CLC Microbial Genomics Module workflow. Candida yeasts were isolated at significantly higher rates from oral rinse and swab samples of OT (68.4%, p < 0.001) and AT (61.9%, p = 0.012) patients, as compared to HC (26.8%). Predominance of Candida albicans specifically, was noted in OT (60.5%, p < 0.001) and AT (42.9%, p = 0.006) vs. HC (9.8%), while non-albicans Candida species was dominant in HC. Analysis of oral mycobiota from OT patients showed the presence of 8 phyla, 222 genera, and 309 fungal species. Low alpha diversity (Shannon index, p = 0.006; Chao-1 biased corrected index, p = 0.01), varied beta diversity (Bray-Curtis, p = 0.01986; Jaccard, p = 0.02766; Weighted UniFrac, p = 0.00528), and increased relative abundance of C. albicans (p = 3.18E-02) was significantly associated with the oral mycobiota of OT vs. HC. This study supported that C. albicans is the main etiological agent in oral thrush and highlights the association of fungal biodiversity with the pathophysiology of oral thrush.
  13. Cheong SC, Selvam B, Ho GF, Muhamad Nor I, Tan CK, Wong YF, et al.
    BMJ Open, 2024 Dec 03;14(12):e076898.
    PMID: 39627139 DOI: 10.1136/bmjopen-2023-076898
    INTRODUCTION: Treatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and gemcitabine (PG) has been shown to be superior to PF in the treatment of R/M nasopharyngeal carcinoma patients. Therefore, we hypothesise that the combination of pembrolizumab with PG would be comparable to pembrolizumab with PF as a first-line treatment in R/M HNSCC.

    METHODS AND ANALYSIS: This is an open-label, multicentre, single-arm, phase 2 study of pembrolizumab plus PG for first-line treatment in subjects with R/M HNSCC in Malaysia. The study is conducted using the Optional Simon optimal 2-stage design. At the initial stage, 26 subjects will be enrolled and if seven or more patients achieve an objective response rate (ORR), then 63 patients will be enrolled. Subjects will be given pembrolizumab 200 mg3 every 3 weeks up to 35 cycles in combination with chemotherapy for up to six cycles of platinum (either cisplatin at 35 mg/m2 intravenous on day 1 and day 8 or carboplatin at area under the curve 5 intravenous on day 1 of each 3-week cycle) and gemcitabine at 1250 mg/m2 intravenous on days 1 and 8 of a 3-week cycle. The primary end point is the ORR as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points include the overall survival, progression free survival, response duration and safety. The exploratory objectives include relationships of microbiome profiles, prognostic and predictive biomarkers with the clinical responses.

    ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the University Malaya Medical Centre (202213-10884). Findings will be disseminated through conference presentations and peer review publications.

    TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (www.

    CLINICALTRIAL: gov); NCT05286619.

  14. Bhoo-Pathy N, Verkooijen HM, Wong FY, Pignol JP, Kwong A, Tan EY, et al.
    Int J Cancer, 2015 Nov 15;137(10):2504-12.
    PMID: 26018878 DOI: 10.1002/ijc.29617
    The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N = 1,138) were included. Survival between patients receiving mastectomy only, breast-conserving therapy (BCT, lumpectomy and adjuvant radiotherapy) and mastectomy with radiotherapy were compared, and adjusted for demography, tumor characteristics and chemotherapy types. Median age at diagnosis was 53 years (range: 23-96 years). Median tumor size at diagnosis was 2.5 cm and most patients had lymph node-negative disease. The majority of patients received adjuvant chemotherapy (n = 861, 76%) comprising predominantly anthracycline-based regimes. In 775 women with T1-2, N0-1, M0 TNBCs, 5-year relative survival ratio (RSR) was highest in patients undergoing mastectomy only (94.7%, 95% CI: 88.8-98.8%), followed by BCT (90.8%, 95% CI: 85.0-94.7%), and mastectomy with radiotherapy (82.3%, 95% CI: 73.4-88.1%). The adjusted risks of mortality between the three groups were not significantly different. In 363 patients with T3-4, N2-3, M0 TNBCs, BCT was associated with highest 5-year RSR (94.1%, 95% CI: 81.3-99.4%), followed by mastectomy with radiotherapy (62.7%, 95% CI: 54.3-70.1%), and mastectomy only (58.6%, 95% CI: 43.5-71.6%). Following multivariable adjustment, BCT and mastectomy with radiotherapy remained significantly associated with lower mortality risk compared to mastectomy only. Overall, adjuvant radiotherapy was associated with higher survival in women aged <40 years, but not in older women. Adjuvant radiotherapy appears to be independently associated with a survival gain in locally advanced as well as in very young TNBC.
  15. Soo JS, Ng CH, Tan SH, Malik RA, Teh YC, Tan BS, et al.
    Apoptosis, 2015 Oct;20(10):1373-87.
    PMID: 26276035 DOI: 10.1007/s10495-015-1158-5
    Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers.
  16. Ho GF, Chai CS, Alip A, Wahid MIA, Abdullah MM, Foo YC, et al.
    BMC Cancer, 2019 Sep 09;19(1):896.
    PMID: 31500587 DOI: 10.1186/s12885-019-6107-1
    BACKGROUND: This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting.

    METHODS: This is a multicenter observational study of first-line afatinib in Malaysian patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). Patients' demographic, clinical and treatment data, as well as resistance mechanisms to afatinib were retrospectively captured. The statistical methods included Chi-squared test and independent t-test for variables, Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis.

    RESULTS: Eighty-five patients on first-line afatinib from 1st October 2014 to 30th April 2018 were eligible for the study. EGFR mutations detected in tumors included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1% of patients. Among these patients, 18.8% had Eastern Cooperative Oncology Group performance status of 2-4, 29.4% had symptomatic brain metastases and 17.6% had abnormal organ function. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Only one-tenth of patients experienced severe side-effects with none having grade 4 toxicities. The objective response rate was 76.5% while the disease control rate was 95.3%. At the time of analysis, 56 (65.9%) patients had progression of disease (PD) with a median progression-free survival (mPFS) of 14.2 months (95% CI, 11.85-16.55 months). Only 12.5% of the progressed patients developed new symptomatic brain metastases. The overall survival (OS) data was not mature. Thirty-three (38.8%) patients had died with a median OS of 28.9 months (95% CI, 19.82-37.99 months). The median follow-up period for the survivors was 20.0 months (95% CI, 17.49-22.51 months). Of patients with PD while on afatinib, 55.3% were investigated for resistance mechanisms with exon 20 T790 M mutation detected in 42.0% of them.

    CONCLUSIONS: Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with a good response rate and long survival, even in patients with unfavorable clinical characteristics. The side-effects of afatinib were manageable and T790 M mutation was the most common resistance mechanism causing treatment failure.

  17. Ang YLE, Ho GF, Soo RA, Sundar R, Tan SH, Yong WP, et al.
    BMC Cancer, 2020 Nov 17;20(1):1118.
    PMID: 33203399 DOI: 10.1186/s12885-020-07616-4
    BACKGROUND: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.

    METHODS: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS).

    RESULTS: We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38-3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14-1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15-3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51-1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792).

    CONCLUSIONS: The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial.

    TRIAL REGISTRATION: The study was registered ( NCT01803503 ) prospectively on clinicaltrials.gov on 4th March 2013.

  18. Tan WL, Chua KLM, Lin CC, Lee VHF, Tho LM, Chan AW, et al.
    J Thorac Oncol, 2020 03;15(3):324-343.
    PMID: 31733357 DOI: 10.1016/j.jtho.2019.10.022
    Stage III NSCLC represents a heterogeneous disease for which optimal treatment continues to pose a clinical challenge. Recent changes in the American Joint Commission on Cancer staging to the eighth edition has led to a shift in TNM stage grouping and redefined the subcategories (IIIA-C) in stage III NSCLC for better prognostication. Although concurrent chemoradiotherapy has remained standard-of-care for stage III NSCLC for almost 2 decades, contemporary considerations include the impact of different molecular subsets of NSCLC, and the roles of tyrosine kinase inhibitors post-definitive therapy and of immune checkpoint inhibitors following chemoradiotherapy. With rapid evolution of diagnostic algorithms and expanding treatment options, the need for interdisciplinary input involving multiple specialists (medical oncologists, radiation oncologists, pulmonologists, radiologists, pathologists and thoracic surgeons) has become increasingly important. The unique demographics of Asian NSCLC pose further challenges when applying clinical trial data into clinical practice. This includes differences in smoking rates, prevalence of oncogenic driver mutations, and access to health care resources including molecular testing, prompting the need for critical review of existing data and identification of current gaps. In this expert consensus statement by the Asian Thoracic Oncology Research Group, an interdisciplinary group of experts representing Hong Kong, Korea, Japan, Taiwan, Singapore, Thailand, Malaysia, and Mainland China was convened. Standard clinical practices for stage III NSCLC across different Asian countries were discussed from initial diagnosis and staging through to multi-modality approaches including surgery, chemotherapy, radiation, targeted therapies, and immunotherapy.
  19. Costas-Chavarri A, Nandakumar G, Temin S, Lopes G, Cervantes A, Cruz Correa M, et al.
    J Glob Oncol, 2019 02;5:1-19.
    PMID: 30802158 DOI: 10.1200/JGO.18.00214
    PURPOSE: To provide resource-stratified, evidence-based recommendations on the treatment and follow-up of patients with early-stage colorectal cancer.

    METHODS: ASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus process with additional experts for one round of formal ratings.

    RESULTS: Existing sets of guidelines from 12 guideline developers were identified and reviewed; adapted recommendations from six guidelines form the evidence base and provide evidence to inform the formal consensus process, which resulted in agreement of 75% or more on all recommendations.

    RECOMMENDATIONS: For nonmaximal settings, the recommended treatments for colon cancer stages nonobstructing, I-IIA: in basic and limited, open resection; in enhanced, adequately trained surgeons and laparoscopic or minimally invasive surgery, unless contraindicated. Treatments for IIB-IIC: in basic and limited, open en bloc resection following standard oncologic principles, if not possible, transfer to higher-level facility; in emergency, limit to life-saving procedures; in enhanced, laparoscopic en bloc resection, if not possible, then open. Treatments for obstructing, IIB-IIC: in basic, resection and/or diversion; in limited or enhanced, emergency surgical resection. Treatment for IIB-IIC with left-sided: in enhanced, may place colonic stent. Treatment for T4N0/T3N0 high-risk features or stage II high-risk obstructing: in enhanced, may offer adjuvant chemotherapy. Treatment for rectal cancer cT1N0 and cT2n0: in basic, limited, or enhanced, total mesorectal excision principles. Treatment for cT3n0: in basic and limited, total mesorectal excision, if not, diversion. Treatment for high-risk patients who did not receive neoadjuvant chemotherapy: in basic, limited, or enhanced, may offer adjuvant therapy. Treatment for resectable cT3N0 rectal cancer: in enhanced, base neoadjuvant chemotherapy on preoperative factors. For post-treatment surveillance, a combination of medical history, physical examination, carcinoembryonic antigen testing, imaging, and endoscopy is performed. Frequency depends on setting. Maximal setting recommendations are in the guideline. Additional information can be found at www.asco.org/resource-stratified-guidelines .

    NOTICE: It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guidelines are intended to complement but not replace local guidelines.

  20. Lopes G, Stern MC, Temin S, Sharara AI, Cervantes A, Costas-Chavarri A, et al.
    J Glob Oncol, 2019 02;5:1-22.
    PMID: 30802159 DOI: 10.1200/JGO.18.00213
    PURPOSE: To provide resource-stratified, evidence-based recommendations on the early detection of colorectal cancer in four tiers to clinicians, patients, and caregivers.

    METHODS: American Society of Clinical Oncology convened a multidisciplinary, multinational panel of medical oncology, surgical oncology, surgery, gastroenterology, health technology assessment, cancer epidemiology, pathology, radiology, radiation oncology, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (Consensus Ratings Group) for two round(s) of formal ratings.

    RESULTS: Existing sets of guidelines from eight guideline developers were identified and reviewed; adapted recommendations form the evidence base. These guidelines, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of 75% or more.

    CONCLUSION: In nonmaximal settings, for people who are asymptomatic, are ages 50 to 75 years, have no family history of colorectal cancer, are at average risk, and are in settings with high incidences of colorectal cancer, the following screening options are recommended: guaiac fecal occult blood test and fecal immunochemical testing (basic), flexible sigmoidoscopy (add option in limited), and colonoscopy (add option in enhanced). Optimal reflex testing strategy for persons with positive screens is as follows: endoscopy; if not available, barium enema (basic or limited). Management of polyps in enhanced is as follows: colonoscopy, polypectomy; if not suitable, then surgical resection. For workup and diagnosis of people with symptoms, physical exam with digital rectal examination, double contrast barium enema (only in basic and limited); colonoscopy; flexible sigmoidoscopy with biopsy (if contraindication to latter) or computed tomography colonography if contraindications to two endoscopies (enhanced only).

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