Phase II study of neoadjuvant chemotherapy with four cycles of dose-dense MVAC followed by radical cystectomy in Korean patients with muscle-invasive or locally advanced urothelial carcinoma of bladder.

PURPOSE: While previous retrospective or phase II studies in Western populations showed that dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) as neoadjuvant chemotherapy (NAC) was beneficial, no studies have been reported in Asian populations. This prospective phase II study aimed to evaluate efficacy and safety of ddMVAC in Korean patients with muscle-invasive bladder cancer (MIBC) or locally advanced urothelial cancer (UC). MATERIALS AND METHODS: Patients with MIBC (cT2-4aN0M0) or locally advanced UC (cTanyN1-3M0) eligible for radical cystectomy (RC) were enrolled prospectively. The participants were treated with four cycles of ddMVAC with pegfilgrastim every 2 weeks. The primary endpoint was pathologic response rate (≤ypT1N0). Secondary endpoints were pathologic complete response (pCR, ypT0N0), relapse-free survival (RFS), overall survival (OS), and safety. RESULTS: Among 24 patients enrolled between December 2019 and August 2021, 23 were evaluable (52%, cT2-4aN0; 48%, cTanyN1-3). Eighteen patients (78%) completed four cycles of ddMVAC, while remaining five patients experienced early discontinuation. Dose modification (91%) and dose delay (70%) occurred, and the dose intensity of ddMVAC was 79%. Nineteen patients underwent RC and four patients declined. Of 19 patients who underwent RC, eight patients (42%) achieved ≤ypT1N0. With a median follow-up of 22.8 months, the median RFS was 13.5 months (95% CI, not yet evaluable) and the median OS was 28.9 months (95% confidence interval, 19.9-37.9). CONCLUSION: Our study showed substantial efficacy and safety of ddMVAC, even in patients with locally advanced UC. The ddMVAC still should be a promising option as NAC in Asian patients with UC.

Differential Prognostic Value of Metabolic Heterogeneity of Primary Tumor and Metastatic Lymph Nodes in Patients with Pharyngeal Cancer.

BACKGROUND/AIM: We aimed to explore the prognostic value of metabolic heterogeneity of 18F-FDG uptake in chemoradiotherapy-treated pharyngeal cancer patients. PATIENTS AND METHODS: This study included 52 consecutive patients with pharyngeal cancer who underwent 18F-FDG PET/CT before definitive chemoradiotherapy. The heterogeneity factor (HF) was defined as the derivative (dV/dT) of a volume-threshold function for primary tumors and metastatic lymph nodes. The relationships between clinical parameters and HFs of primary tumors (pHF) and metastatic lymph nodes (nHF) were analyzed. RESULTS: The pHF (range=∓1.367 - -0.027; median=-0.152) was significantly correlated with the maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis. Induction chemotherapy response was not correlated with HF, whereas response to radiotherapy was significantly better in patients with high pHF (low heterogeneity). Consistently, the 2-year locoregional recurrence-free survival was significantly better in patients with high pHF (82.9% for pHF>-0.152 vs. 30.5% for pHF<-0.152, log-rank p=0.009). The nHF (range=-1.067 - -0.039; median=-0.160) was not correlated with response to radiotherapy and locoregional recurrences. CONCLUSION: pHF, but not nHF, was a significant predictor of response to radiotherapy and locoregional recurrence in pharyngeal cancer. Thus, HF use can prevent unnecessary treatment and surgical delays.

The role of surgical clips in the evaluation of interfractional uncertainty for treatment of hepatobiliary and pancreatic cancer with postoperative radiotherapy.

PURPOSE: To evaluate the utility of implanted surgical clips for detecting interfractional errors in the treatment of hepatobiliary and pancreatic cancer with postoperative radiotherapy (PORT). METHODS AND MATERIALS: Twenty patients had been treated with PORT for locally advanced hepatobiliary or pancreatic cancer, from November 2014 to April 2016. Patients underwent computed tomography simulation and were treated in expiratory breathing phase. During treatment, orthogonal kilovoltage (kV) imaging was taken twice a week, and isocenter shifts were made to match bony anatomy. The difference in position of clips between kV images and digitally reconstructed radiographs was determined. Clips were consist of 3 proximal clips (clip_p, ≤2 cm) and 3 distal clips (clip_d, >2 cm), which were classified according to distance from treatment center. The interfractional displacements of clips were measured in the superior-inferior (SI), anterior-posterior (AP), and right-left (RL) directions. RESULTS: The translocation of clip was well correlated with diaphragm movement in 90.4% (190/210) of all images. The clip position errors greater than 5 mm were observed in 26.0% in SI, 1.8% in AP, and 5.4% in RL directions, respectively. Moreover, the clip position errors greater than 10 mm were observed in 1.9% in SI, 0.2% in AP, and 0.2% in RL directions, despite respiratory control. CONCLUSION: Quantitative analysis of surgical clip displacement reflect respiratory motion, setup errors and postoperative change of intraabdominal organ position. Furthermore, position of clips is distinguished easily in verification images. The identification of the surgical clip position may lead to a significant improvement in the accuracy of upper abdominal radiation therapy.

Maximum Standardized Uptake Value of Pelvic Lymph Nodes in [18F]-Fluorodeoxyglucose Positron Emission Tomography Is a Prognostic Factor for Para-Aortic Lymph Node Recurrence in Pelvic Node-Positive Cervical Cancer Treated With Definitive Chemoradiotherapy.

OBJECTIVES: This study aimed to identify prognostic factors for para-aortic lymph node (PALN) recurrence and their effect on survival outcomes in patients with pelvic node-positive squamous cell carcinoma (SCC) of the cervix treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: Of the 116 patients with biopsy-proven SCC of the uterine cervix who underwent primary CCRT from 2007 to 2012, 48 patients with pelvic LN metastasis detected by [F]-fluorodeoxyglucose positron emission tomography (FDG PET) were retrospectively analyzed. Patients with evidence of para-aortic lymphadenopathy were excluded. The whole pelvis was the standard irradiation field for all patients. The associations of age, stage, serum SCC antigen (SCC-Ag) level, maximum standardized uptake value (SUVmax), hemoglobin level, overall treatment time, adjuvant chemotherapy, and pelvic LN status with PALN recurrence and survival outcomes were evaluated. RESULTS: At a median follow-up of 34.0 months (range, 8-73 months), 10 (20.8%) patients had developed PALN recurrences. The relationship between pelvic LN FDG uptake and PALN recurrence was evaluated by the cutoff value (SUVmax = 3.85) determined by receiver operating characteristic curve analysis. The independent risk factors for PALN recurrence were FDG-avid pelvic LN (SUVPLN) greater than 3.85 (hazard ratio, 13.12; P = 0.025) and posttreatment SCC-Ag level greater than 2.0 (ng/mL) (hazard ratio, 20.69; P = 0.019). Patients with an SUVPLN greater than 3.85 were found to have significantly worse 5-year distant metastasis-free (51.0% vs 79.0%, P = 0.016) and progression-free survival (38.7% vs 67.3%, P = 0.011) than those with an SUVPLN less than or equal to 3.85. CONCLUSIONS: SUVPLN is a statistically significant prognostic factor of PALN recurrence and survival after definitive CCRT for pelvic node-positive SCC of the uterine cervix.

Analysis of the prognostic factors for distant metastasis after induction chemotherapy followed by concurrent chemoradiotherapy for head and neck cancer.

PURPOSE: The aim of this study is to identify the prognostic factors of distant metastasis (DM) after induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) for locoregionally advanced head and neck cancer (HNC). MATERIALS AND METHODS: A total of 321 patients with HNC who underwent IC followed by CRT treated between January 2005 and December 2010 were analyzed retrospectively. IC consisted of three courses of docetaxel (70 mg/m(2)) and cisplatin (75 mg/m(2)) every three weeks, followed by radiotherapy of 66-70 Gy/2 Gy per fraction/5 fractions per week concurrent with weekly cisplatin (40 mg/m(2)). Tumor/nodal stage, primary site, tumor differentiation, lower neck node involvement (level IV, VB, and supraclavicular regions), number of concurrent chemotherapy cycles, overall duration of radiotherapy, and response to IC were assessed as potential prognostic factors influencing DM and survival outcome. RESULTS: The five-year loco-regional recurrence and DM rates were 23.6% and 18.2%. N stage, overall duration of radiotherapy, lower neck node involvement, and response to IC were significant factors for DM. With a median follow-up period of 52 months (range, 4 to 83 months), the 5-year progression-free, DM-free, and overall survival rates were 41.2%, 50.7%, and 55.1%, respectively. Lower neck node involvement (p=0.008) and poor response to IC (p < 0.001) showed an association with significantly inferior DM-free survival. CONCLUSION: Even with the addition of IC, the DM rate and survival outcome were poor when metastatic lower neck lymph nodes were present or when patients failed to respond after receiving IC.

Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma.

PURPOSE: We sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma. MATERIALS AND METHODS: We retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders. RESULTS: Thirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008). CONCLUSION: Conformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.

Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer.

PURPOSE: The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. MATERIALS AND METHODS: Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m(2)) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. RESULTS: At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. CONCLUSION: Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens.

Short-course palliative radiotherapy for uterine cervical cancer.

PURPOSE: The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. MATERIALS AND METHODS: Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. RESULTS: The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. CONCLUSION: Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.