Head and Neck Cancer of Unknown Primary: A Multicenter Retrospective Cohort study in Northern Thailand, an Endemic Nasopharyngeal Cancer Area.

OBJECTIVE: This study aimed to evaluate the characteristics and oncological outcomes of head and neck carcinoma of unknown primary (HNCUP) patients in an endemic nasopharyngeal cancer (NPC) area. METHODS: One hundred and forty-four HNCUP patients curatively treated between January 1995 and December 2022 from 5 centers were retrospectively recruited onto the study to analyze the clinicopathological characteristics and oncological outcomes and compare them with historical data. A multivariate Cox proportional hazards model analysis was performed to evaluate factors affecting survival outcomes. A propensity-matched pair analysis of the patients with positive and negative EBV-encoded small RNA (EBER) staining was applied to compare the characteristics and outcomes between the two groups. RESULTS: The median follow-up time was 45 months. Most patients (88.2%) received total mucosal irradiation (TMI). Primary tumor emergence (PTE) was detected in 6 patients (4.2%) who did not have TMI. The 5-year overall survival (OS), disease-free survival, and locoregional recurrence-free survival were 51.3%, 64.9%, and 72.7%, respectively. Extranodal extension and N3 compared with the N1 stage were the significant independent predictors for OS (HR 2.90, 95% CI 1.12-7.51, p = 0.028 and HR 3.66, 95%CI 1.23-11.89, p = 0.031, respectively). The matched-pair analysis demonstrated comparable all survival outcomes between the EBER-positive and -negative groups. All patients in the matched pair analysis received TMI, and no PTE was detected. CONCLUSION: Our survival outcomes were comparable to previous studies with a low rate of PTE. The matched pair analysis of EBER-positive and -negative groups revealed similar oncological outcomes and no primary tumor emergence when total mucosal irradiation was administered.

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.