Wimrak Onchan

Current evidence of temozolomide and bevacizumab in treatment of gliomas

Abstract Objective: This review article summarizes in vitro, in vivo, and clinical evidence pertaining to temozolomide (TMZ) and bevacizumab (BEV) efficacy and mechanism of action in gliomas. Methods: Relevant publications published before June 2013 in PubMed database were reviewed. Results: Temozolomide and BEV are current chemotherapeutic agents treating patients with high-grade glioma, including glioblastoma. In vitro and in vivo studies have proposed discordant cell death pathways for TMZ as either apoptosis or autophagy using different experimental setting details or cell lines. In addition, BEV may cause cell death through hypoxia-induced autophagy or unspecific indirect effects on cancer cells. The complexity of cancer cells in glioma has contributed to their resistance of both chemotherapies. In clinical trials, overall survival duration in glioma patients with recurrence (8–9 months) is lower than that in newly diagnosed patients (12–15 months). Conclusion: Our collected data support the addition of radiotherapy, BEV, and other targeted agents to TMZ treatment, indicating prolonged survival duration in newly diagnosed patients. However, the optimal regimen for treating high-grade glioma cannot be concluded without more clinical trials.

Image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiotherapy (WP-IMRT) for locally advanced cervical cancer: a prospective study from Chiang Mai University Hospital, Thailand

Purpose A report of preliminary results and toxicity profiles using image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiation therapy (WP-IMRT) for locally advanced cervical cancer. Material and methods Fifteen patients with locally advanced cervical cancer were enrolled into the study. WP-IMRT was used to treat the Clinical Target Volume (CTV) with a dose of 45 Gy in 25 fractions. Concurrent cisplatin (40 mg/m2) was prescribed during radiotherapy (RT) on weekly basis. IGBT using computed tomography was performed at the dose of 7 Gy × 4 fractions to the High-Risk Clinical Target Volume (HR-CTV). Results The mean cumulative doses – in terms of equivalent dose of 2 Gy (EQD2) – of IGBT plus WP-IMRT to HR-CTV, bladder, rectum, and sigmoid colon were 88.3, 85.0, 68.2 and 73.6 Gy, respectively. In comparison with standard (point A prescription) dose-volume histograms, volume-based image-guided brachytherapy improved the cumulative doses for bladder of 67%, rectum of 47% and sigmoid of 46%. At the median follow-up time of 14 months, the local control, metastasis-free survival and overall survival rates were 93%, 100% and 93%, respectively. No grade 3-4 acute and late toxicities were observed. Conclusion The combination of image-guided brachytherapy and intensity-modulated radiotherapy improved the dose distribution to tumor volumes and avoided overdose in OARs which could be converted in excellent local control and toxicity profiles.

Two-year results of transabdominal ultrasound-guided brachytherapy for cervical cancer

PURPOSE To report the preliminary results of transabdominal ultrasound (TAUS)-guided brachytherapy (BT) in cervical cancer. METHODS AND MATERIALS Twenty-nine patients with cervical cancer Stage IB-IVA according to The International Federation of Gynecology and Obstetrics staging were treated by radical radiotherapy from February 2012 to December 2012. Treatment was composed of WPRT to 50 Gy in 25 fractions and central shielding after 44 Gy in combination with TAUS-guided BT to optimize the total dose (equivalent dose of 2 Gy [EQD2]) to the minimal dose at cervical points (in EQD2 concepts) defined by TAUS ≥80 Gy while maintaining low doses to the ICRU report no. 38 bladder and rectal points. The treatment results and toxicity profiles were reported. RESULTS At median followup time of 19 months (range, 17-27), the local control and disease-free survival rates were 93.1% and 86.2%, respectively. One episode of Grade 3 vaginal toxicity was observed in this followup period. The mean applied doses to cervix, bladder, and rectal points were 82.6, 72.5, and 75 Gy, respectively. TAUS-guided planning reduced bladder (defined as >80 Gy in EQD2) and rectal overdose (defined as >75 Gy in EQD2) in 44.9% and 34.5% of patients, respectively. CONCLUSION The 2-year results demonstrate that TAUS-guided BT is feasible and associated with excellent tumor control/toxicity rates in cervical cancer.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

The effect of central shielding in the dose reporting for cervical cancer in EQD2 era.

Purpose To evaluate the cumulative dose at point A for three and four centimeters central shielding. Material and methods The plans of external beam radiotherapy plus conventional intracavitary brachytherapy were performed. Three or four centimeters central shieldings (after 44 Gy) were applied to the standard whole pelvis irradiation. Additional intracavitary brachytherapy 4 × 7 Gy at point A was prescribed, and the cumulative dose in EQD2 (α/β = 10) of 3 cm and 4 cm central shielding were evaluated. Results The cumulative dose at point A in EQD2 (α/β = 10) of 3 cm central shielding were 95.7 Gy for AR and 95.5 Gy for AL, while the cumulative dose at point As in EQD2 (α/β = 10) of 4 cm central shielding were 90.8 Gy for AR and 91.2 Gy for AL. Conclusions The 3 cm central shielding caused higher cumulative dose (in terms of EQD2 [α/β = 10]) than 4 cm central shielding.

A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer.

The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose–volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm3 (30.5%) and 5.4 cm3 (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6–5.9 Gy, P < 0.001 and 2.1–9.9 Gy, P < 0.001, respectively). The Dmean of the contralateral parotid decreased in 70% of the patients (range, 0.2–4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC.

Real-world outcomes of postmastectomy radiotherapy in breast cancer patients with 1–3 positive lymph nodes: a retrospective study

Objective: To assess the treatment outcomes and to explore the determinants of clinical outcome in breast cancer patients with 1–3 positive nodes who did or did not receive postmastectomy radiotherapy (PMRT) in a tertiary care referral cancer center in Northern Thailand. Methods: We investigated a retrospective cohort of registered breast cancer patients at the Faculty of Medicine, Chiang Mai University, Thailand from 2001–2007. Analysis was performed using Cox regression models to identify factors affecting the overall survival (OS) and relapse-free survival (RFS) rates. Comparisons were made between two cohorts: women who received adjuvant PMRT (74 patients) and women who did not receive adjuvant PMRT (81 patients). Results: A total of 155 patients were included with a median follow-up period of 4.45 years. There was a statistically significant 4-year OS difference between the two groups of patients: 100% for the PMRT group and 93.1% for the non-PMRT group (P = 0.044). The 4-year RFS was 85.9% for patients receiving PMRT and 78.3% for patients who did not receive PMRT (P = 0.291). On multivariate analysis of OS, using hormonal treatment was the only significant independent factor associated with improved OS. On multivariate analysis of RFS, none of the variables were significantly associated with improved RFS. PMRT was notfound to be a prognostic variable related to the outcome of patients using a logistic regression model. Conclusion: Our retrospective, hospital-based analysis demonstrated that PMRT improved the treatment outcome in terms of OS for women with 1–3 node positive early-stage breast cancer.

Outcome of eribulin as a late treatment line for Thai metastatic breast cancer patients

Background We report the safety and efficacy of eribulin as a late treatment line in Thai metastatic breast cancer (MBC) patients. Patients and methods A total of 30 MBC patients treated with eribulin between January 2014 and January 2017 were retrospectively analyzed. The patients were scheduled to receive 1.4 mg/m2 of eribulin on day 1, day 8 and subsequently every 21 days. All patients had previously received at least three chemotherapy regimens including anthracycline and taxane. Response rate and progression-free survival (PFS) were analyzed. Results The median age was 56 years (range, 40–74 years), with a median follow-up time of 5.7 months (range, 0.2–25 months). The overall response rate was 30% (nine patients): four patients had triple-negative breast cancer, three patients had luminal B breast cancer and two patients had luminal A breast cancer. The median PFS was 2.9 months (range, 0.2–14 months). The median number of previous chemotherapy regimens was 4 (range, 3–9). Univariate analysis showed that the number of regimens (four or fewer) prior to eribulin was statistically associated with superior PFS (P = 0.009). Multivariate analysis also showed similar statistical association between number of prior regimens (four or fewer) and better PFS adjusted by age group (≥50 years; hazard ratio = 1.29; 95% CI: 1.0–1.65; P = 0.046). There were no toxic deaths or grade 4 toxicities. Nine (30%) patients had grade 3 anemia toxicities, and the other common toxicities were leukopenia and neutropenia. Four (13%) patients required dose reduction and 16 (53%) patients required dose delay because of toxicities. Conclusion Eribulin is an effective drug for heavily pretreated MBC patients with tolerable toxicities. The benefit was superior in patients who received fewer than four previous chemotherapy regimens.

Intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer

OBJECTIVES To report the intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer. MATERIALS AND METHODS Ninety-two patients with cervical cancer (stage IB-IVA, according to FIGO staging), were treated by curative radiotherapy from February 2012 to June 2015. All patients were treated with whole pelvic radiotherapy to 50 Gy in 25 fractions and central shielding after 44 Gy, in combination with TAUS-guided brachytherapy, in order to escalate the total dose (EQD2) to the minimal dose at cervical points (in EQD2 concepts) defined by TAUS, while maintaining low doses to ICRU bladder and rectal points. The treatment results and toxicity profiles were reported. RESULTS At median follow-up time of 41.2 months (range 8 to 61 months) the pelvic control, disease-free survival, and overall survival rates were 84.8%, 75%, and 88%, respectively. The mean applied doses to cervix, bladder, and rectal points were 83.5, 72.3, and 76.5 Gy, respectively. Eight patients developed grade 2 Gastrointestinal toxicity. CONCLUSION The 3-year results demonstrated that TAUS-guided brachytherapy is feasible and associated with excellent tumor control/toxicity rates in cervical cancer.

The outcome of the first 100 nasopharyngeal cancer patients in Thailand treated by Helical Tomotherapy

Abstract Background The aim of the study was to analyse of two-year loco-regional failure free survival (LRFFS), distant metastasis free survival (DMFS), overall survival (OS), and toxicity outcomes of the first 100 nasopharyngeal carcinoma patients in Thailand treated by helical tomotherapy. Patients and methods Between March 2012 and December 2015, 100 patients with non-metastatic nasopharyngeal carcinoma were treated by helical tomotherapy. All patients were treated by platinum-based concurrent chemoradiotherapy and adjuvant or neo-adjuvant chemotherapy. Results The median age was 51 years (interquartile ranges [IQR]: 42.5–57.0). The mean ± SD of D95% of planning target volume (PTV) 70, 59.4 and 54 were 70.2 ± 0.5, 59.8 ± 0.6, and 54.3 ± 0.8 Gy, respectively. The mean ± SD of conformity index, and homogeneity index were 0.89 ± 0.13 and 0.06 ± 0.07. Mean ± SD of D2 % of spinal cord and brainstem were 34.1 ± 4.4 and 53.3 ±6.3 Gy. Mean ± SD of D50 of contralateral and ipsilateral parotid gland were 28.4 ± 6.7 and 38.5 ± 11.2 Gy. At a median follow-up of 33 months (IQR: 25–41), the 2-year LRFFS, DMFS, OS were 94% (95%CI: 87–98%), 96% (95% CI: 89–98%), and 99% (95% CI: 93–100%), respectively. Acute grade 3 dermatitis, pharyngoesophagitis, and mucositis occurred in 5%, 51%, and 37%, respectively. Late pharyngoesophagitis grade 0 and 1 were found in 98% and 2% of patients. Late xerostomia grade 0, 1 and 2 were found in 17%, 78% and 5%, respectively. Conclusions Helical tomotherapy offers good dosimetric performance and achieves excellent treatment outcome in nasopharyngeal carcinoma patients.