Effect of postoperative radiotherapy for patients with differentiated thyroid cancer.

OBJECTIVE: We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features. MATERIALS AND METHODS: This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years. RESULTS: After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported. CONCLUSION: PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT.

The effect of comprehensive oral care program on oral health and quality of life in patients undergoing radiotherapy for head and neck cancer: A quasi-experimental case-control study.

OBJECTIVES: The purpose of this study is to investigate the effect of the comprehensive oral care program on oral health status and symptoms in head and neck cancer (HNC) patients undergoing radiotherapy. METHODS: This was a quasi-experimental study using a non-equivalent control group in non-synchronized design. All participants including control and experimental group were asked for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N35 (EORTC QLQ-H&N35) and given an oral health education 4 times at baseline, immediate postradiotherapy, 3 months after radiotherapy, and 6 months after radiotherapy. In each visit except for final, the experimental group was given fluoride varnish application and fluoride mouth rinsing solution for daily use. Oral health examination for dental caries, plaque score (PS), bleeding on probing (BOP), and salivary flow rate was performed in baseline and 6 months after radiotherapy. Statistical analyses were done by paired t-tests and mixed ANCOVA repeated-measures analysis. RESULTS: From November 1, 2013 to October 31, 2015, a total 61 patients undergoing radiotherapy for HNC cancer were enrolled (30 in control and 31 in experimental groups). Decrease in salivary flow rate was comparable between 2 groups. Dental caries increased in control group (P = .006); PS and BOP were decreased in experimental group (P < .001 and .004, respectively). Experimental group showed lower swallowing, speech problems, and less sexuality scores in EORTC QLQ-H&N35 than control group. CONCLUSION: We found improvement in oral health and the quality of life in HNC patients with comprehensive oral care intervention by dental professionals. Communicating and cooperating between the healthcare and dental professionals is needed to raise the quality of health care services for HNC patients receiving radiotherapy.

Quantitative Estimation of the Equivalent Radiation Dose Escalation using Radiofrequency Hyperthermia in Mouse Xenograft Models of Human Lung Cancer.

Hyperthermia is a potent radiosensitizer, and its effect varies according to the different types of cancer cells. In the present study, the radiosensitizing effect of hyperthermia on lung cancer cell lines A549 and NCI-H1299 was determined based on the equivalent radiation dose escalation. In vitro cell experiments were conducted using lung cancer cell lines A549 and NCI-H1299 to determine thermal radiosensitivity. In vivo experiments were conducted using mouse heterotopic xenograft models to determine the treatment response and increase in the temperature of tumors using a 13.56 MHz radiofrequency (RF) hyperthermia device. Using the α and ß values of the linear-quadratic equations of cell survival curves, numerical simulations were performed to calculate the equivalent radiation dose escalations. The dielectric properties of tumors were measured, and their effect on the calculated equivalent radiation dose was analyzed. Hyperthermia increased the equivalent radiation dose of lung cancer xenografts and a higher escalation was found in NCI-H1299 cells compared with that observed in A549 cells. An underestimation of the calculated equivalent radiation dose was observed when the dielectric property of the tumor was varied. This study may contribute to the effective planning of thermoradiotherapy in clinics.

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: a role in organ preservation.

BACKGROUND/AIMS: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. METHODS: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. RESULTS: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). CONCLUSIONS: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.

Changes of Clinicopathologic Characteristics and Survival Outcomes of Anaplastic and Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: This study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC). METHODS: A retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci. RESULTS: The five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; p < 0.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; p < 0 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, p = 0.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (p = 0.013). CONCLUSIONS: The choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer.

20 year experience of postoperative radiotherapy in IB-IIA cervical cancer patients with intermediate risk factors: impact of treatment period and concurrent chemotherapy.

OBJECTIVE: To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors. METHODS: Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n=56) or CCRT (n=54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n=39), RT 2000-2010 (n=17) and CCRT 2000-2010 (n=54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n=48). RESULTS: Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p=0.012) and distant metastasis (p=0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p<0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups. CONCLUSIONS: This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.

Immunohistochemical study identifying prognostic biomolecular markers in nasopharyngeal carcinoma treated by radiotherapy.

BACKGROUND: We evaluated the predictive significance of 14 reported markers using immunohistochemical study in nasopharyngeal carcinoma. METHODS: Immunohistochemical stainings were done in 38 patients for Met, cyclooxygenase-2 (COX-2), nm23-H1, epidermal growth factor receptor (EGFR), p63, early growth response factor 1 (Egr1), chromosome segregation 1-like (CSE1L), cathepsin-D (aspartyl protease), C-erbB2, p53, signal transducers and activators of transcription (STAT3/STAT5), CD138 (Syndecan-1), and LIN28 with the usual methods. RESULTS: The median follow-up time was 30 months (11-83 months). High Met and CD138 expression were statistically significant negative prognostic factors on survival. The expression of Egr1 had a positive prognostic effect on survival. The combined score of these 3 markers, Met plus CD138 minus Egr1, was a strong prognostic factor. The median survival curve was distinctly separated in accord with this combined score. No prognostic value was revealed in COX-2, nm23-H1, EGFR, p63, CSE1L, cathepsin-D, C-erbB2, p53, STAT3, STAT5, and LIN28. CONCLUSIONS: The combined score of these markers could be used to stratify biomolecular risk groups.

Long-term survival of resectable subset after induction chemotherapy in patients with locally advanced head and neck cancer.

BACKGROUND: Although meta-analysis showed that survival improved with concurrent chemoradiation in locally advanced head and neck cancer, neoadjuvant chemotherapy is still unique, because it renders curative surgery feasible for marginally resectable head and neck cancer patients. METHODS: We reviewed patients with locally advanced head and neck cancer, who had been treated with neoadjuvant chemotherapy between June 1984 and February 2001 at the Seoul National University Hospital. RESULTS: A total of 167 patients were included. After 2 to 3 chemotherapy cycles, either surgery (38 patients) or radiation (104 patients) was conducted. Those who received surgery exhibited better survival than those who received radiation [median survival: not reached vs 33.6 months (95% CI: 22.6-44.7), p = .006]. The 5-year and 10-year survival rates of surgery group were 63.2% and 59.8%. CONCLUSION: The potential benefit of neoadjuvant chemotherapy with surgery in patients with locally advanced head and neck cancers merits further evaluation in future clinical trials.

Preliminary results of pre-radiation neck dissection in head and neck cancer patients undergoing organ preservation treatment.

CONCLUSION: Pre-RT ND in patients with HNSCC undergoing organ preservation treatment is safe, advantageous, poses no additional morbidity owing to the elective neck dissection, and may possibly improve survival outcomes. OBJECTIVE: Establish the role of pre-radiation neck dissection (pre-RT ND) in patients with head & neck squamous cell carcinoma (HNSCC) undergoing organ preservation treatment. MATERIALS AND METHODS: Fourteen patients with histologically confirmed HNSCC in stages III approximately IV with proven regional metastasis were enrolled in the organ preservation approach incorporating pre-RT ND at a tertiary referral center between May 1998 and August 2004. Site matched patients treated with organ preservation intent in the conventional fashion were used as controls. Data were collected for their diagnosis, management, treatment outcome, and follow up. RESULTS: Disease free survival was significantly better for the pre-RT ND group. There was no significant difference in overall survival, pattern of recurrence, and primary organ preservation rate between the two groups. No significant morbidity owing to neck dissection was noted in patients who underwent neck dissection. Although the delivery of radiation to the primary site was delayed for patients in the pre-RT ND group, it did not influence the major outcomes.

Neoadjuvant chemotherapy followed by radiotherapy in epidermoid carcinoma of anus.

AIM AND BACKGROUND: The purpose of this study was to analyze the efficacy of neoadjuvant fluorouracil-cisplatin chemotherapy combined with radiotherapy for anal cancer. METHODS: Fourteen patients with epidermoid carcinoma of the anal canal were analyzed. Treatment consisted of three cycles of 5-fluorouracil (1000 mg/m2 bolus on days 1-5) and cisplatin (60 mg/m2 bolus on day 1) followed by 50.4 Gy to the pelvis and perineum over 5.5 weeks. Both inguinal lymphatics were irradiated with an identical dose schedule. The median follow-up was 78 months. RESULTS: Five-year overall survival rate and sphincter preservation rate was 85.1% and 85.7%, respectively. Response to chemoradiotherapy was the only significant factor with univariate analysis (P = 0.031). There were no complications of RTOG grade 3 or higher. CONCLUSIONS: Neoadjuvant chemotherapy with a cisplatin-based regimen rather than concurrent regimen plus radiotherapy may decrease complications without compromising survival or sphincter preservation.

High cyclooxygenase-2 expression is related with distant metastasis in cervical cancer treated with radiotherapy.

PURPOSE: The cyclooxygenase (COX)-2 enzyme has been shown to have an important role in carcinogenesis and apoptosis in various types of cancer. The purpose of this study was to evaluate the relationship between local recurrence or distant metastasis and COX-2 expression and apoptosis in cervical cancer patients treated with radical radiotherapy (RT). METHODS AND MATERIALS: Twenty-two patients who were diagnosed with cervical cancer were enrolled in this study. All patients were treated with radical RT (external beam RT plus brachytherapy) at Seoul National University Hospital. The formalin-fixed, paraffin-embedded tissues of 11 patients who developed local recurrence (n = 3) or distant metastasis (n = 8) were compared with those of other patients who were disease free. Prognostic factors, including tumor size, lymph node metastatic status, and stage, were well balanced between the two groups. COX-2 expression was determined immunohistochemically, and apoptosis was assessed using in situ DNA nick end labeling (TUNEL)-based methods. RESULTS: COX-2 expression was stronger in the local recurrence and distant metastasis patients than in those free of disease. COX-2 expression was shown to have a statistically significant influence on treatment failure by the Mann-Whitney U test (p = 0.015) and the Mantel-Haenszel chi-square test (p = 0.015), but its distribution did not correlate with apoptosis. Among the clinicopathologic factors, including stage, lymph node metastatic status, and tumor size, lymph node metastatic status was found to closely correlate with COX-2 expression by the Mann-Whitney U test (p = 0.045) and Mantel-Haenszel chi-square test (p = 0.065). CONCLUSION: COX-2 is believed to be one of the important factors associated with lymph node involvement and treatment failure. Our results suggest that inhibiting COX-2 may decrease treatment failure in cervical cancer treated with RT, and that COX-2 inhibitor administration may play an adjuvant role in cervical cancer treatment.