Salvage Treatment and Outcomes of Locally Advanced Cervical Cancer after Failed Concurrent Chemoradiation with or without Adjuvant Chemotherapy: Post Hoc Data Analysis from the ACTLACC Trial.

OBJECTIVES: To evaluate the type of salvage treatment and outcomes of patients with locally advanced cervical cancer who failed treatment with concurrent chemoradiation with or without adjuvant chemotherapy. METHODS: This was post hoc analyses of data from the randomized trial which included 259 patients who had FIGO stage IIB-IVA and had either pelvic radiation therapy concurrent with cisplatin followed by observation or paclitaxel plus carboplatin. Data of the patients who failed primary treatment were collected: type of salvage treatments, time to progress after salvage therapy, progression-free (PFS) and overall survivals (OS). RESULTS: After primary treatment, 85 patients had either persistence (36.5%), progression (18.8%), or recurrences (44.7%). The sites of failure were loco/regional in 52.9%, systemic failure in 30.6%, and loco-regional and systemic in 16.5%. Chemotherapy was given in 51.8%, being the sole therapy in 34.1%. Majority were combination agents (31.8%), with paclitaxel/carboplatin as the most common regimen. Radiation to the metastatic sites along with chemotherapy was used in 14.1% whereas palliative radiation therapy or supportive care was used in approximately 10% of each. The median time from the start of salvage treatment to progression was 9.2 months (range 0.2-64.0 months) with median PFS of 11.2 months (95% CI, 7.2-15.3 months). Median overall survival 27.3 months (95% CI, 4.4-69.6 months). CONCLUSIONS: Chemotherapy, either alone or with radiation therapy, was the most common salvage treatment in LACC after failure from primary treatment. The time to progress and PFS were less than 1 year with OS of approximately 2 years.

Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial.

OBJECTIVES: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.

Cost-utility analysis of adjuvant chemotherapy after concurrent chemoradiation in patients with locally advanced cervical cancer.

INTRODUCTION: This study aimed to compare the cost utility of concurrent chemoradiation (CCRT) to CCRT followed by adjuvant chemotherapy (CCRT/ACT) in locally advanced cervical cancer (LACC) using provider and societal viewpoints. METHODS: Data from our trial which was a multi-centre study evaluating the efficacy of ACT compared to CCRT/ACT were entered into a decision tree model. The data included clinical probability, direct medical and non-medical costs, and utility obtained from the patients. The total cost, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were estimated for a time horizon of 3 years. All costs and outcomes were discounted at 3% annually. RESULTS: The cost of CCRT and CCRT/ACT was approximately 3,058 and 6,896 USD and 4,309 and 7,480 USD from provider and from societal viewpoints, respectively. The QALYs for CCRT and CCRT/ACT were 2.31480 and 2.32045, respectively. The ICER was 569,575 USD per QALY. For stage III-IVA LACC, the ICER was 28,050 USD per QALY. In the sensitivity analysis, the cost of ACT was the most significant influential parameter on the ICER. The ICER would be 0.26-fold lower if the cost of ACT was reduced by 25%. At the current ceiling threshold of 5,000 USD/QALY, CCRT had a 100% probability of being the best option. CONCLUSIONS: In the Thai context, CCRT is more cost effective than CCRT/ACT for stage IIB-IVA LACC. CCRT/ACT may be considered only for stage III-IVA LACC because it has a lower ICER than other types of LACC.

A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial.

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had International Federation of Gynecology and Obstetrics stage IIB-IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82-1.96; p=0.293) and 1.42 (95% CI=0.81-2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164, Thai Clinical Trials Registry Identifier: TCTR 20140106001.

Treatment outcomes of high-dose-rate intracavitary brachytherapy for cervical cancer: a comparison of Ir-192 versus Co-60 sources.

OBJECTIVE: To determine and compare treatment outcomes between cobalt-60 (Co-60) and iridium-192 (Ir-192) high dose rate (HDR) brachytherapy in stage IB2-IIIB cervical cancer patients at Department of Radiology, Faculty of Medicine Vajira Hospital, Navamindrahiraj University. METHODS: A retrospective cohort study of patients diagnosed with cervical cancer and treated with radiotherapy at the Department of Radiation Oncology, Faculty of Medicine Vajira Hospital between 2004 and 2014. Survival rate was analyzed by Kaplan-Meier method and were compared between groups with log-rank test. Multivariate analysis was performed using Cox proportional hazards model. RESULTS: A total of 480 patients with cervical cancer and treated with radiotherapy were included, 274 patients for Ir-192 group and 206 patients for Co-60 group. The 2- and 5-year disease-free survival rate in Ir-192 group were 80.4% and 73.1% and in Co-60 group were 82.5% and 74.7%, respectively (p=0.365). Overall survival rates at 2 and 5 years were 89.4% and 77% of the Ir-192 group, and 91.6% and 81.9% in the Co-60 group, respectively (p=0.238). The complications were primarily grade 1 or 2. Grade 3 and 4 complications were found in 13 of 274 and 7 of 206 in Ir-192 and Co-60 groups, respectively (p=0.232). Grade and clinical stage of cancer significantly affected the survival outcome. CONCLUSION: Cervical cancer patients who were treated with HDR Co-60 brachytherapy were comparable in survival and toxicity outcomes of those with HDR Ir-192 brachytherapy. Co-60 source has lots of economic advantages over Ir-192 and hence suitable for low resource radiotherapy setting.

Treatment outcomes of concurrent weekly carboplatin with radiation therapy in locally advanced cervical cancer patients.

OBJECTIVE: To evaluate treatment outcomes of locally advanced cervical cancer patients who received concurrent weekly carboplatin with radiation therapy. METHODS: Patients with locally advanced cervical cancer who had primary radiation treatment in concurrent with weekly carboplatin (100mg/m(2) or AUC 2) from 1997 to 2008 were identified. Demographic data, chemotherapy cycles, total treatment time, toxicities, and treatment outcomes were recorded. RESULTS: One hundred and forty-eight patients with stage IIB (50.7%), IIIB (48.0%) and IVA (1.3%) cervical cancer patients were included in the study. Median total treatment time was 53.5 days (range, 45-100 days). Carboplatin was given for a median number of 6 cycles (range, 3-6 cycles). Complete response was achieved in 142 patients (95.9%) while six (4.1%) had persistent diseases. Among the 142 responders, 36 experienced recurrences: pelvic recurrences in seven (4.7%), distant failure in 25 (16.9%), and both pelvic and distant in four (2.7%). The 2-year and 5-year progression-free survival rates were 75.1% and 63.0%, respectively with the corresponding 2-year and 5-year overall survival rates of 81.9% and 63.5%. No grade 3 or 4 hematologic and non-hematologic toxicities were observed during treatment in any patients. Late grade 3-4 gastrointestinal or genitourinary toxicities were 10.1% and 0.7%, respectively. CONCLUSION: Concurrent weekly carboplatin with radiation therapy yields high response rate with modest progression-free and overall survivals in locally advanced cervical cancer. The regimen is feasible with minimal toxicities.

Pretreatment levels of serum vascular endothelial growth factor do not correlate with outcome in patients with locally advanced cervical cancer.

OBJECTIVE: To evaluate pretreatment levels of serum VEGF in locally advanced cervical cancer patients, and assess any association with clinocopathological parameters and response to radiotherapy. METHODS: Patients with histologically proven and diagnosed locally advanced cervical cancer or stages IIB-IVA were included in this study. Blood serum was obtained by peripheral venous puncture about 24 hours before the beginning of radiotherapy. All patients were followed up at one and three month intervals from the last day of the complete treatment for evaluating the responses to radiotherapy. RESULTS: Mean age of the 40 patients was 52.8 ± 11.1 years. Sixty percent were in stage IIB and 90% had squamous cell carcinoma. The median pretreatment level of serum VEGF was 611.3 pg/ml (0.00-4,067 pg/ml). The pretreatment levels of serum VEGF did not correlate with stage (p=0.75), tumor histology (p=0.91), tumor size (p=0.46) or tumor characteristics (p=0.49). Almost all patients received concurrent chemoradiation as a curative treatment, with a complete response found in 94.9%. Values for patients who were completed response was rather lower than in patients with persistent disease, but without statistical significance (581.4 pg/ml vs 759.6 pg/ml, p=0.37). CONCLUSION: Pretreatment levels of serum VEGF do not correlate with clinicopathological factors or response to radiation therapy.

Treatment outcomes and prognostic factors of patients with breast cancer: a retrospective review.

OBJECTIVE: To determine overall survival (OS), disease-free survival (DFS), and prognostic factors for survival in patients with invasive breast cancer treated with combined-modality therapy at BMA Medical College and Vajira Hospital. MATERIAL AND METHOD: The authors retrospectively analyzed the patient-tumor characteristic and treatment outcomes of 615 patients with invasive breast cancer who were treated in our radiation oncology division between 1997 and 2006. The authors used the Kaplan-Meier method to describe OS and DFS. The authors analyzed associations of patients and tumor characteristics with OS using the log-rank test and Cox proportional hazards models. RESULTS: The median follow-up time of 60 months, there were 46 loco-regional relapses, 108 distant relapses, and 129 deaths. The 5-year OS and DFS were 77.5% and 73.8%, respectively. The median times to local recurrence (LR) and to distant recurrence (DR) were 23 months (range, 10-67 months) and 24 months (range, 5-91 months). Characteristic statistically significant associated with decreased OS included lymphocascular invasion (LVI), estrogen receptor (ER) and progesterone receptor (PR) status, tumor stage, nodal stage, lymph node involvement > or =20%, and stage of disease. CONCLUSION: Overall, the prognosis of patients with breast cancer was good However the subgroup of patients who presented with LVI, ER, and PR negative, T3-4 stage, N3-nodal stage, lymph node involvement > OR =20%, and higher stage of disease had a poor long-term outcome.

Dosimetric study of inverse-planed intensity modulated, forward-planned intensity modulated and conventional tangential techniques in breast conserving radiotherapy.

OBJECTIVE: The authors present the result of a dosimetric comparison of inverse-planed intensity modulated, forward-planned intensity modulated, and conventional tangential technique in breast conserving radiotherapy. METHOD AND MATERIAL: The breasts (Right side: Left side = 1:1), heart, and lungs of 28 patients were contoured on all the computed tomography (CT)-slice. Three different treatment plans were created: (1) inverse IMRT (iIMRT), (2) forward IMRT (fIMRT), and (3) conventional tangential technique (CVT). The total prescribed dose for all plans was 50 Gy/25 fractions. All treatment plans were normalized at 95% of the prescribed dose covered the entire PTV and used inhomogeneity corrections. RESULTS: For the entire group, the mean breast volume was 517 cc. The V105% for iIMRT, fIMRT and conventional plans was 1.12%, 2.36% and 16.81%, which iIMRT better than fIMRT and CVT (p < 0.001) and fIMRT better than CVT (p < 0.05). The Dmax for the iIMRT plan received 105.03%, which was significantly less than those from the fIMRT(106.6%, p < 0.001) and the conventional (110.68%, p < 0.001) plan. The PTV coverage (V95-105%) for the iIMRT, fIMRTand conventional was 96%, 91% and 87%, which iIMRT better than fIMRT and CVT (p < 0.05) and fIMRT better than CVT (p < 0.05). The PTV CI for the iIMRT technique was 0.704, which was significantly more conformity than those from the fIMRT (0.639, p < 0.001) and the conventional (0.539, p < 0.001) techniques. The PTV CI of fIMRT is significantly better than CVT (p < 0.005). Mean ipsilateral lung dose was 642.7 cGy, 747.6 cGy and 882.25 cGy for iIMRT fIMRT and CVT respectively (p < 0.05) The V20Gy reduced from 14.87% for conventional plan to 12.82% for the fIMRT plan, while 0.88% was obtained for the iIMRT plan (P<0.05). The heart V30 Gy value was 3.124%, 4.65%, and 5.84% for iIMRT, fIMRT and conventional plans, respectively (p < 0.05). The mean dose of contralateral breast was 55.86 cGy, 60.33 cGy, 68.57 cGy for iIMRT, fIMRT and conventional plans, respectively (p < 0.05 both). The mean contralateral lung dose was 57.8 cGy, 43.87 cGy, and 32.28 cGy for iIMRT, fIMRT and conventional plans, respectively (p < 0.005 both). CONCLUSION: The iIMRT technique provides significantly improved PTV Dmax, PTV V105%, PTV V110%, target volume coverage, dose homogeneity and dose conformity throughout the target volume of breast and reduced doses to all critical structures, compared to the fIMRT and conventional techniques. In view of fIMRT technique, it significantly improved the dose distribution and reduced dose to OARs compared to conventional technique, although not better than iIMRT technique.

Efficacy of various synthetic pyrethroid-impregnated encasement materials against house dust mite under laboratory conditions.

The acaricidal activity of synthetic pyrethroid and benzyl benzoate against Dermatophagoides pteronyssinus was examined in the laboratory, using a specially designed test set up. On the basis of median lethal dose (LD50) values, the compound found to be most toxic to D. pteronyssinus was benzyl benzoate (LD50 = 50 mg/m2), followed by permethrin (LD50 = 76.7 mg/m2), deltamethrin (LD50 = 146.7 mg/m2), esbioallenthrin (LD50 = 186.6 mg/m2) and lamdacyhalothrin (LD50 = 756.6 mg/m2). Very low toxicity was observed with bifenthrin (LD50 = 5157.8 mg/m2). A laboratory control trial was also carried out to compare the acaricidal activity (residual effect) of four pyrethroids impregnated on woven and non-woven encasement materials against house dust mites during a 4-month period. Of the pyrethroids used in this study, esbioallenthrin demonstrated the highest acaricidal activity, and of the pyrethroid impregnated materials, the non-woven encasement material was more effective than the woven encasement material.