Search

Purpose The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea.Materials and Methods Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals.Results Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001).Conclusion In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

The value of squamous-cell carcinoma antigen (SCC-Ag) as a tumor marker for cervical cancer is controversial because it is not elevated (> 2 ng/mL) in a quarter of patients at diagnosis. Two hundred ninety one IB-IVA cervical squamous cell-carcinoma patients who underwent definitive chemoradiotherapy (CRT) were included in four tertiary institutions. Serum conversion pattern between pre- and post-treatment SCC-Ag levels was categorized into the following three arms: (1) Consistent Seronegative arm (both ≤ 2 ng/mL); (2) Negative Conversion arm (from > 2 ng/mL to ≤ 2 ng/mL); and (3) Consistent Seropositive arm (both > 2 ng/mL). Median follow-up time was 40.3 months. For Consistent Seronegative (N = 67), Negative Conversion (N = 165), and Consistent Seropositive (N = 59) arms, the 3-year recurrence-free survival (RFS) rates were 79.4%, 62.0%, and 48.4% (P

Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available.

BACKGROUND This study aimed to evaluate whether computed tomography (CT)-based volumetric body composition analysis has prognostic value in head and neck cancer (HNC) patients. METHODS This single-center retrospective study included 79 patients with HNC treated with definitive radiotherapy from March 2009 to December 2018. The patients were assessed for (a) weight-based variables and (b) pretreatment and posttreatment CT-based body composition variables. Overall survival (OS) and recurrence-free survival (RFS) analyses were conducted using Cox proportional hazards analyses. RESULTS Depletion of cervical skeletal muscle volume on presentation was associated with poor OS (hazard ratio [HR] = 3.1; 95% CI = 1.2-7.8; P = .016). Low fat proportions before and after treatment were associated with poor OS (HR = 2.5-3.5; 95% CI = 1.3-9.3; P = .013-.026). In multivariate Cox analysis, increased posttreatment fat attenuation demonstrated the greatest prognostic value for both OS (HR = 4.7; 95% CI = 2.2-10.3; P

The role of radiosurgery has become further accentuated in the era of targeted agents (TA). Thus, the neurologic outcome of radiosurgery in brain metastasis (BM) of non-small cell lung cancer (NSCLC) was reviewed. We analyzed 135 patients with BM of NSCLC who were administered Cyberknife radiosurgery (CKRS) as either initial or salvage therapy. We evaluated local failure (LF), intracranial failure (IF), and neurological death (ND) due to BM. Primary outcome was neurological death-free survival (NDFS). Median follow-up was 16.2 months. Median CKRS dose of 22 Gy was administered to median 2 targets per patient. Among 99 deaths, 14 (14%) were ND. Upfront treatment for BM included CKRS alone in 85 patients (63%), CKRS + TA in 26 patients (19%), and WBRT in 24 patients (18%). No patients or tumor related factors were associated with ND. However, the type of upfront treatment for BM was significantly associated with ND [HR 0.07 (95% CI 0.01–0.57) for CKRS + TA, HR 0.56 (95% CI 0.19–1.68) for CKRS alone] compared with the WBRT group (P = 0.01). The 2-year NDFS rates for the CKRS + TA, CRKS alone, and WBRT groups were 94%, 87%, and 78%, respectively (P = 0.03). Upfront CKRS showed significantly higher 2-year LF-free survival rate (P

Aim To investigate predictive and prognostic role of metabolic parameters using [18 F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG PET) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with docetaxel-platinum induction chemotherapy (IC). Methods Medical records of 31 patients with pre- and post-IC 18 F-FDG PET were reviewed. Using 18 F-FDG PET, metabolic parameters, including metabolic tumor response, adjusted peak standardized uptake values using lean body mass at baseline (pre-SULpeak ) and after IC (post-SULpeak ), and percentage change of pre- and post-SULpeak (ΔSULpeak ), were assessed. Results Response rate (RR) was 71%, with a metabolic RR of 83.9%. Nineteen (61.3%) patients underwent surgery, R0 resection was achieved for 17 (89.5%) patients. Median relapse-free survival (RFS) and overall survival (OS) were 8.9 months (95% CI: 4.5-12.1) and 24.1 months (95% CI: 17.1-34.1), respectively. Post-SULpeak 1.4 could predict recurrence with a sensitivity of 84% and a specificity of 100%. Conclusion In patients with locally advanced NSCLC receiving IC, post-SULpeak and ΔSULpeak showed clinical significance for survival outcome.

Objectives The pathologic nodal stage of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) patients is classified according to the number of lymph nodes (LNs), as revised in 2018. Previous studies showed that the LN ratio (LNR) could be also a significant prognostic factor in head and neck cancer, but there are few studies on the LNR in HPV-related [HPV(+)] OPC. The aim of the present study was to analyze the predictive value of the LNR for survival and recurrence in HPV(+) OPC patients. Materials and methods HPV(+) OPC patients treated with surgery with or without postoperative radiotherapy from January 2000 to March 2019 were evaluated. The patients were divided into two sets of three groups, according to LN numbers based on pathologic nodal stages, and LNRs by a cutoff value of 0.05. The medical records were reviewed, and the overall survival (OS), disease-free survival, locoregional recurrence, and distant metastasis incidence were analyzed. Results Ninty patients were included and the median follow-up period was 38.2 months. There were no significant differences in OS in the LN number groups. However, there was a significant difference in OS in the LNR groups (P = 0.010). The incidence of distant metastasis in the LNR groups was significantly different (P = 0.005). Conclusion The LNR in HPV(+) OPC patients may be a more useful tool to predict survival and distant metastasis than the LN number. Additional research and consensus on surgical pathology are needed before applying the LNR to adjuvant treatment decisions and pathologic nodal staging.

This study aimed to evaluate the oncologic outcomes according to disease burden in uterine cervical cancer patients with metachronous distant metastases.Between 2005 and 2015, 163 patients with metachronous distant metastases from uterine cervical cancer after receiving a definitive therapy were evaluated at seven institutions in Korea. Low metastatic burden was defined as less than 5 metastatic sites, whereas high metastatic burden was others. Each metastasis site was divided based on the lymph node (LN) and organs affected. The overall survival (OS) and progression-free survival (PFS) were assessed. Cox proportional hazards models, including other clinical variables, were used to evaluate the survival outcomes.The median follow-up duration was 22.2 months (range: 0.3-174.8 months). Para-aortic LNs (56.4%), lungs (26.4%), supraclavicular LNs (18.4%), and peritoneum (13.5%) were found to be the common metastasis sites. Among 37 patients with a single metastasis, 17 (45.9%) had LN metastases and 20 (54.1%) had organ metastases. The 1- and 2-year OS rates were 73.9% and 55.0%, respectively, whereas the PFS rates were 67.2% and 42.9%, respectively. SCC Ag after recurrence and high metastatic burden were significant factors affecting the OS (p=0.004 and p0.001, respectively). Distant organ recurrence, short disease-free interval (≤2 years), and high metastatic burden were unfavorable factors for PFS (p=0.003, p=0.011, and p=0.002, respectively).A favorable oncologic outcome can be expected by performing salvage treatments in selected patients with a long disease-free interval, low metastatic burden, and/or lymphatic-only metastasis.

We evaluated whether there is a difference in the local recurrence and survival after pelvic external radiotherapy (ERT) with and without boost vaginal brachytherapy (VB) in cervical cancer patients with positive or close vaginal resected margins (RM). We retrospectively reviewed FIGO stage IA-IIB cervical cancer patients treated with postoperative ERT between 1997 and 2018. The sixty patients showing close (safety margin

Purpose: Studies on de-escalation in radiation therapy (RT) for human papillomavirus-related (HPV(+)) oropharyngeal cancer (OPC) are currently ongoing. This study investigated the current practice regarding the radiation dose and field in the treatment of HPV(+) OPC.Materials and Methods: The Korean Society for Head and Neck Oncology conducted a questionnaire on the primary treatment policy. Among them, for HPV(+) OPC scenarios, radiation oncologists were questioned regarding the field and dose of RT.Results: Forty-two radiation oncologists responded to the survey. In definitive concurrent chemoradiotherapy (CCRT) treatment for stage T2N1M0 OPC, most respondents prescribed a dose of >60 Gy to the primary tonsil and involved ipsilateral lymph nodes. However, eight of the respondents prescribed a relatively low dose of ≤54 Gy. For stage T2N1M0 OPC, postoperative adjuvant RT was prescribed by eight and nine respondents with a lower dose of ≤50 Gy for the ipsilateral tonsil and involved neck, respectively. In definitive CCRT in complete remission after induction chemotherapy for initial stage T2N3M0 OPC, de-escalation of the tonsil and involved neck were performed by eight and seven respondents, respectively. Regarding whether de-escalation is applied in radiotherapy for HPV(+) OPC, 27 (64.3%) did not do it at present, and 15 (35.7%) were doing or considering it.Conclusion: The field and dose of prescribed treatment varied between institutions in Korea. Among them, dose de-escalation of RT in HPV(+) OPC was observed in approximately 20% of the respondents. Consensus guidelines will be set in the near future after the completion of ongoing prospective trials.

Purpose Thoracic re-irradiation (re-RT) of lung cancer has been challenged by the tolerance doses of normal tissues. We retrospectively analyzed local control, overall survival (OS) and toxicity after thoracic re-RT using highly conformal radiotherapy, such as intensity modulated radiotherapy and stereotactic body radiotherapy. Materials and methods Thirty-one patients who received high-dose thoracic re-RT were analyzed. Doses were recalculated to determine biologically equivalent doses. The median interval to re-RT was 15.1 months (range, 4.4 to 56.3 months), the median initial dose was 79.2 Gy10 (range, 51.75 to 150 Gy10), and the median re-RT dose was 68.8 Gy10 (range, 43.2 to 132 Gy10). Results Eighteen (58.1%) and eleven (35.5%) patients showed loco-regional recurrence and distant metastasis, respectively, after 17.4 months of median follow-up. The 1-year and 2-year local control rates were 60.2% and 43.7%, respectively. The median loco-regional recurrence-free-survival (LRFS) was 15.4 months, and the median OS was 20.4 months. The cumulative and re-RT biologically equivalent dose for α/β=10 (BED10) doses were the most significant prognostic factors. Cumulative BED10 ≥145 Gy10 and re-RT BED10≥68.7 Gy10 were significantly associated with longer OS (p=0.029 and p=0.012, respectively) and LRFS (p=0.003 and p=0.000, respectively). The most frequent acute toxicity was grade 1-2 pulmonary toxicity (41.9%). No acute grade 3 or higher toxicities occurred. Conclusion Our results show that high-dose thoracic re-RT of lung cancer can be safely delivered using highly conformal radiotherapy with favorable survival and acceptable toxicity. An optimal strategy to select patients who would benefit from re-RT is crucial in extending the indications and improving the efficacy with a sufficiently high dose.

Purpose The purpose of this study is to evaluate the safety and efficacy of the multimodality treatment with neoadjuvant intensity-modulated radiotherapy (IMRT) for resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM). Materials and Methods A total of eleven patients who received neoadjuvant chemotherapy and radiotherapy between March 2016 and June 2018 were reviewed. Patients received 25 Gy in 5 fractions to entire ipsilateral hemithorax with helical tomotherapy. Results All of patients were men with a median age of 56 years. Epithelioid subtype was found in 10 patients. All patients received neoadjuvant chemotherapy with pemetrexed-cisplatin regimen. Ten patients (90.9%) completed 25 Gy/5 fractions and one (9.0%) completed 20 Gy/4 fractions of radiotherapy. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed 1 week (median, 8 days; range, 1 to 15 days) after completing IMRT. Extrapleural pneumonectomy was performed in 4 patients (36.3%), extended pleurectomy/decortication in 2 (18.2%) and pleurectomy/decortications in 5 (63.6%). There was no grade 3+ surgical complication except two deaths after EPP in 1 month. Based on operative findings and pathologic staging, adjuvant chemotherapy was delivered in 7 patients (63.6%), and 2 (18.2%) were decided to add adjuvant radiotherapy. After a median follow-up of 14.6 months (range, 2.8 to 30 months), there were 3 local recurrence (33.3%) and 1 distant metastasis (11.1%). Conclusion Neoadjuvant entire pleural IMRT can be delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies are needed to look at long-term outcomes.

During hyperthermia therapy, cancer cells are heated to a temperature in the range of 40 ~ 45 °C for a defined time period to damage these cells while keeping healthy tissues at safe temperatures. Prior to hyperthermia therapy, the amount of heat energy transferred to the cancer cells must be predicted. Among various non-invasive methods, the thermal prediction method using the specific absorption rate (SAR) is the most widely used method. The existing methods predict the thermal distribution by using a single constant for the mass density in one organ through assignment. However, because the SAR and the bio heat equation (BHE) vary with the mass density, the mass density of each organ must be accurately considered. In this study, the mass density distribution was calculated using the relationship between the Hounsfield unit and the mass density of tissues in preceding research. The SAR distribution was found using a quasi-static approximation to Maxwell’s equation and was used to calculate the potential distribution and the energy distributions for capacitive RF heating. The thermal distribution during exposure to RF waves was determined by solving the BHE with consideration given to the considering contributions of heat conduction and external heating. Compared with reference data for the mass density, our results was within 1%. When the reconstructed temperature distribution was compared to the measured temperature distribution, the difference was within 3%. In this study, the density distribution and the thermal distribution were reconstructed for the agar phantom. Based on these data, we developed an algorithm that could be applied to patients.

Background: Studies on de-escalation in radiation therapy (RT) for human papillomavirus-related [HPV(+)] oropharyngeal cancer (OPC) are currently ongoing. This study investigated the current practice regarding the radiation dose and field in the treatment of HPV(+) OPC.Methods: The subcommittee on Oropharyngeal Cancer Treatment Guidelines of the Korean Society for Head and Neck Oncology (KSHNO) conducted a questionnaire on the primary treatment policy in five scenarios. Among them, for HPV(+) OPC scenarios, radiation oncologists were questioned regarding the field and dose of RT.Results: Forty-two radiation oncologists responded to the survey. In definitive concurrent chemoradiotherapy (CCRT) treatment for stage T2N1M0 OPC, most respondents prescribed a dose of >60 Gy to the primary tonsil and involved ipsilateral lymph nodes (LNs). However, eight of the respondents prescribed a relatively low dose of ≤54 Gy. Various doses were prescribed for the non-involved chain, and 50 and 54 Gy were the most commonly selected doses. For stage T2N1M0 OPC, postoperative adjuvant RT was prescribed by eight and nine respondents with a lower dose of ≤50 Gy for the ipsilateral tonsil and involved neck, respectively. In definitive CCRT in complete remission after induction chemotherapy for initial stage T2N3M0 OPC, most respondents included the contralateral LNs with less de-escalated radiation fields. De-escalation of the tonsil and involved neck were performed by eight and seven respondents, respectively. Regarding whether de-escalation is applied in radiotherapy for HPV(+) OPC, 27 (64.3%) did not do it at present, and 15 (35.7%) were doing or considering it.Conclusions: The field and dose of prescribed treatment varied between institutions in Korea. Among them, dose de-escalation of RT in HPV(+) OPC was observed in approximately 20% of the respondents. Consensus guidelines will be set in the near future after the completion of ongoing prospective trials.

Background Positron-emission tomography (PET) is widely used to detect malignancies, but consensus on its prognostic value in oropharyngeal cancer has not been established. The purpose of this study was to analyze the PET parameters associated with tumor extent and survival in resectable oropharyngeal cancer. Methods The PET parameters in oropharyngeal cancer patients with regional node metastasis who underwent surgery and postoperative radiotherapy between January 2005 and January 2019 were analyzed. We calculated the SUVmax, tumor-to-liver ratio (TLR), metabolic tumor volume (MTV, volume over SUV 2.5), and total lesion glycolysis (TLG, MTV x mean SUV) of the primary lesion and metastatic nodes. Histologic findings, patient survival, and recurrence were reviewed in the medical records. Results Fifty patients were included, and the PET parameters were extracted for 50 primary lesions and 104 nodal lesions. In the survival analysis, MTV and TLG of the primary lesions showed significant differences in overall survival (OS) and recurrence-free survival (RFS). In the multiple regression analysis, TLG of the primary lesion was associated with the depth of invasion (DOI). MTV of the nodes was a significant factor affecting extranodal extension (ENE). Conclusions PET parameters could be related with OS, RFS, DOI of the primary tumor, and ENE. PET would be expected to be a useful diagnostic tool as a prognosticator of survival and pathologic findings in oropharyngeal cancer.

BackgroundHypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in rapid tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.MethodsA xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.ResultsShort-term treatment with IR alone and CKD-516 + IR (d1) significantly reduced tumor volume (p = 0.006 andp = 0.048, respectively). Treatment with CKD-516 + IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516 + IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516 + IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).ConclusionsTaken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.

Objectives We assessed the role of adjuvant chemotherapy (ACT) in patients with advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy (CCRT) and investigated the prognostic factors for recurrence and survival. Materials and Methods Between January 2008 and January 2018, 88 non-metastatic nasopharyngeal carcinoma patients treated with CCRT and with or without ACT in two institutions were retrospectively reviewed. The initial tumor response evaluation was performed 1 month after CCRT completion. Survival analysis was performed for factors such as initial tumor regression, ACT and other clinical factors. Subgroup analysis was performed for the four-group categorized according to tumor regression and ACT (CR with/without ACT, non-CR with/without ACT). Results Complete response (CR) 1 month after CCRT was a favorable prognosticator for progression-free survival (PFS) (hazard ratio [HR] 3.16, 95% confidence interval [CI] 1.02–9.85, p = 0.046) and overall survival (OS) (HR 3.19, 95% CI 1.14–8.93, p = 0.027). Also, ACT was an independent factor for PFS (HR 0.38, 95% CI 0.15–0.98, p = 0.047) and OS (HR 0.37, 95% CI 0.13–0.99, p = 0.047). In subgroup analysis, the CR after CCRT followed by ACT group showed significantly higher locoregional recurrence-free survival (p = 0.02), OS (p = 0.003), distant-metastasis free survival (p = 0.07), and PFS (p = 0.01) than the other three groups. Conclusion Tumor regression 1 month after CCRT, and administration of ACT identified as an independent prognosticator for PFS and OS in this study. Even patients who show early tumor regression after CCRT may benefit from ACT. Further randomized trials should define the role of ACT in patients with nasopharyngeal cancer who achieved CR after CCRT.

Purpose The benefits of reirradiation for head and neck cancer (HNC) have not been determined. This study evaluated the efficacy of reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent or second primary HNC (RSPHNC) and identified subgroups for whom reirradiation for RSPHNC is beneficial. Materials and methods A total of 118 patients from seven Korean institutions with RSPHNC who underwent IMRT-based reirradiation between 2006 and 2015 were evaluated through retrospective review of medical records. We assessed overall survival (OS) and local control (LC) within the radiotherapy (RT) field following IMRT-based reirradiation. Additionally, the OS curve according to the recursive partitioning analysis (RPA) suggested by the Multi-Institution Reirradiation (MIRI) Collaborative was determined. Results At a median follow-up period of 18.5 months, OS at 2 years was 43.1%. In multivariate analysis, primary subsite, recurrent tumor size, interval between RT courses, and salvage surgery were associated with OS. With regard to the MIRI RPA model, the class I subgroup had a significantly higher OS than class II or III subgroups. LC at 2 years was 53.5%. Multivariate analyses revealed that both intervals between RT courses and salvage surgery were prognostic factors affecting LC. Grade 3 or more toxicity and grade 5 toxicity rates were 8.5% and 0.8%, respectively. Conclusion IMRT-based reirradiation was an effective therapeutic option for patients with RSPHNC, especially those with resectable tumors and a long interval between RT courses. Further, our patients' population validated the MIRI RPA classification by showing the difference of OS according to MIRI RPA class.

Purpose We conducted this study to evaluate the outcomes of external-beam radiotherapy tumor boost (EBRT-B) in cervical cancer patients who could not receive intracavitary brachytherapy. Methods A total of 11 hospitals provided the data of patients who received EBRT-B during the period from January 2005 through October 2012. Results A total of 75 patients were included. The median radiotherapy dose was 46 Gy (range, 40–54 Gy) for whole pelvis and 24 Gy (range, 9–35 Gy) for EBRT-B. Initial tumor responses assessed at 2 to 6 months after radiotherapy were as follows: 46 with complete response, 22 with partial response, 2 with stable disease, and 3 with progressive disease. After a median follow-up time of 33 months, 30 patients (40.0%) showed disease progression including 21 (28.0%) with local progression. The 5-year local failure-free survival rate was 70.0%. Achieving complete response at the first follow-up visit and an overall treatment time of 53 days or less were significantly related to favorable local failure-free survival. The rate of grade 3 or higher toxicity was 2.6%. Conclusions Approximately 70% of patients had local tumor control after curative radiotherapy using EBRT-B. Early tumor response and overall treatment time of 53 days or less were closely associated with favorable local control.

Objectives: Despite complete surgical resection, 30–40% of patients with stage I–IIA non-small-cell lung cancer (NSCLC) have recurrences. We aimed to elucidate the effect of lymphovascular invasion (LVI) on the prognosis and patterns of recurrence in patients with pathologically confirmed T1–2N0 NSCLC. Methods: We evaluated 381 patients who underwent complete resection and were diagnosed with pathologic T1–2N0 NSCLC between March 2000 and January 2012. Local recurrence, nodal recurrence, and distant metastasis were defined and analyzed. Results: LVI was present in 72 patients (18.9%). The 5-year disease-free survival (DFS) for all patients was 69.9%. Patients with LVI showed a significant decrease in 5-year DFS (47.3 vs. 74.4%, p < 0.001). LVI was a significant prognostic predictor in multivariate analysis (p = 0.003). The patients with LVI showed a significantly increased 5-year cumulative incidence of nodal recurrence (22.5 vs. 8.7%, p < 0.001) and distant metastasis (30.4 vs. 14.9%, p = 0.004). However, no difference was shown between the two groups in the 5-year cumulative incidence of local recurrence (p = 0.416). Conclusions: LVI is a negative prognostic factor in patients with stage I–IIA NSCLC. The presence of LVI significantly increases the risk of nodal and distant recurrence.

PURPOSE To investigate the predictive role of maximum standardized uptake value (SUVmax) of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS Between October 2006 and April 2016, 53 patients were treated with IMRT in two institutions and their PET/CT at the time of diagnosis was reviewed. The SUVmax of their nasopharyngeal lesions and metastatic lymph nodes (LN) was recorded. IMRT was delivered using helical tomotherapy. All patients except for one were treated with concurrent chemoradiation therapy (CCRT). Correlations between SUVmax and patients' survival and recurrence were analyzed. RESULTS At a median follow-up time of 31.5 months (range, 3.4 to 98.7 months), the 3-year overall survival (OS) and disease-free survival (DFS) rates were 83.2% and 77.5%, respectively. In univariate analysis, patients with a higher nodal pre-treatment SUVmax (≥ 13.4) demonstrated significantly lower 3-year OS (93.1% vs. 55.5%; p = 0.003), DFS (92.7% vs. 38.5%; p < 0.001), locoregional recurrence-free survival (100% vs. 50.5%; p < 0.001), and distant metastasis-free survival (100% vs. 69.2%; p = 0.004), respectively. In multivariate analysis, high pre-treatment nodal SUVmax (≥ 13.4) was a negative prognostic factor for OS (hazard ratio [HR], 7.799; 95% confidence interval [CI], 1.506-40.397; p = 0.014) and DFS (HR, 9.392; 95% CI, 1.989-44.339; p = 0.005). CONCLUSIONS High pre-treatment nodal SUVmax was an independent prognosticator of survival and disease progression in nasopharyngeal carcinoma patients treated with IMRT in our cohort. Therefore, nodal SUVmax may provide important information for identifying patients who require more aggressive treatment.

Objective The aim of this multi-institutional study was to determine the prognostic impact of tumour parameters, such as tumour size (TS), tumour volume (TV), and marker expression, on survival during radiation therapy (RT) for cervical cancer patients. Methods A total of 231 patients with histologically confirmed cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) Ib2-IVa, were enrolled in this study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) and squamous cell carcinoma antigen (SCC-ag) analysis were performed twice, during RT and just before brachytherapy. Results The median follow-up time was 27.8months (range, 2–116months). Multivariate analysis revealed that stage (odds ratio [OR], 2.936 and 95% confidence interval [CI], 1.119–7.707; P =0.029), tumour volume reduction rate (TVRR) (OR, 3.435 and 95% CI, 1.062–11.106; P =0.039), and SCC-ag reduction rate (SCCRR) (OR, 5.104 and 95% CI, 1.769–14.727; P =0.003) were independently associated with overall survival (OS), while pre-RT TS (OR, 2.148 and 95% CI, 1.221–3.810; P =0.009), mid-RT TV (OR, 3.106 and 95% CI, 1.685–5.724; P P =0.016) were associated with progression-free survival (PFS). Based on the prognostic factor analysis, patients with the highest prognostic risk score of 3 showed poorer overall survival and progression free survival than patients with lower prognostic risk scores. Conclusion We identified that tumour parameters such as TVRR, SCCRR, pre-RT TS, and mid-RT TV areindependent and strong prognostic parameters for patients with cervical cancer receiving RT. This scoring system-based prognostic factor analysis could be used to help develop optimized treatment plans for cervical cancer patients during RT.

Highlights • The current study extracted radiomics—a large quantitative data of imaging features—from magnetic resonance images of patients with nasopharyngeal carcinoma. • The survival model fitted with radiomic features showed good prognostic performance in predicting the progression-free survival of patients with nasopharyngeal carcinoma (integrated area under the curve, 0.71; 95% confidence interval, 0.71–0.72). • Addition of radiomics to clinical survival model improved the prognostication of progression-free survival in patients diagnosed with nasopharyngeal carcinoma (integrated area under the curve from 0.76 to 0.81, p, Objectives To assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) Methods Patients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. Results This study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72–0.80; p=0.04), stage (iAUC, 0.70–0.79; p=0.001), and combined models (iAUC, 0.76–0.81; p

Spindle assembly checkpoint (SAC) prevents mis-segregation of chromosome and allows accurate division in mitosis. Mps1 (also known as TTK) is one of the essential kinases for recruitment of SAC proteins after chromosome segregation. Failure of SAC induces chromosome instability, mitotic catastrophe, and ultimately apoptotic cell death and Mps1 is induced or activated in rapidly dividing tumor cells. Therefore, Mps1 has been considered an attractive anti-cancer drug target. VRN081569 is a potent type I kinase inhibitor of Mps1, which stabilizes Mps1 kinase domain in a closed conformation by forming a tight interface with its kinase domain. This structural stabilization appears to increase cellular potency for the induction of aneuploidy and apoptosis (~ 10 nM or less GI50 value). The loss of retinoblastoma tumor suppressor gene (Rb1), which is prevalent in advanced cancers, dysregulates cell cycle and promotes cell division. In particular, the resistance to CDK4/6 inhibitors has been reportedly mediated by loss of the Rb1 gene. We found that Rb1-negative cells express higher level of Mps1 than Rb1-positive cells and VRN081569 efficiently induce apoptosis of Rb1-negative Triple Negative Breast Cancer (TNBC) cell line MDA-MB-468 than Rb1-positive TNBC MDA-MB-231. Especially we confirmed that VRN081569 induces caspase 3/7 activity faster in Rb1-negative cells (~50-fold EC50 of caspase 3/7 activity compared to Rb1-positive cells), and cell cycle analysis has shown that our compound induces a dose-dependent dysregulation of mitosis, resulting in a decrease in the frequency of the G0/G1 phase, and also induces aneuploidy and apoptosis. Finally, we confirmed a combination effects with anti-microtubule agents BCL-2 inhibitor and PARP-1 inhibitor, suggesting that modulation of two different cellular processes may overcome the lack of single agent activity for TNBC. Citation Format: Hong Ryul Jung, Yeonsil Kim, Haelee Kim, Ji-Hye Kwon, Dong-hyuk Seo, Jung Beom Son, Nam Doo Kim, Daekwon Kim, Sunghwan Kim. VRN08, a Selective Mps1 Kinase Inhibitor Induces Mitotic Catastrophe and Apoptosis Efficiently in Advanced Cancers Including Rb1-Deficient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB119.

Purpose The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively. Materials and Methods Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patients were identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test. Results The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groups were similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively. Conclusion INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.

Locoregional failure is the most frequent pattern of failure in locally advanced head and neck cancer patients and it leads to death in most of the patients. Second primary tumors occurring in the other head and neck region reach up to almost 40% of long-term survivors. Recommended and preferred retreatment option in operable patients is salvage surgical resection, reporting a 5-year overall survival of up to 40%. However, because of tumor location, extent, and underlying comorbidities, salvage surgery is often limited and compromised by incomplete resection. Reirradiation with or without combined chemotherapy is an appropriate option for unresectable recurrence. Reirradiation is carefully considered with a case-by-case basis. Reirradiation protocol enrollment is highly encouraged prior to committing patient to an aggressive therapy. Radiation doses greater than 60 Gy are usually recommended for successful salvage. Despite recent technical improvement in intensity-modulated radiotherapy (IMRT), the use of concurrent chemotherapy, and the emergence of molecularly targeted agents, careful patient selection remain as the most paramount factor in reirradiation. Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of chemoradio-resistant clonogens. Treatment protocols that combine novel targeted radiosensitizing agents with conformal high precision radiation are required to overcome the resistance while minimizing toxicity. Recent large number of data showed that IMRT may provide better locoregional control with acceptable acute or chronic morbidities. However, additional prospective studies are required before a definitive conclusion can be drawn on safety and effectiveness of IMRT.

Purpose This study aimed to investigate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with locally advanced non-small cell lung cancer (NSCLC) who received concurrent chemoradiotherapy (CCRT). Materials and Methods We retrospectively analyzed 66 patients with locally advanced NSCLC treated with definitive CCRT. Among these patients, 95% received paclitaxel/carboplatin or docetaxel/cisplatin. The median radiation dose was 66 Gy in 33 fractions. The NLR and PLR before/after CCRT were evaluated. The maximally selected log-rank test was used to obtain the cutoff values related to the overall survival (OS). Results Patients with high post-CCRT NLR (>3.12) showed worse OS, locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) than those with low NLR (2-year OS: 25.8% vs. 68.2%, p < 0.001; 2-year LRPFS: 12.9% vs. 33.8%, p = 0.010; 2-year DMFS: 22.6% vs. 38.2%, p = 0.030). Patients with high post-CCRT PLR (>141) showed worse OS and LRPFS than those with low PLR (2-year OS: 37.5% vs. 71.1%, p = 0.004; 2-year LRPFS: 16.5% vs. 40.3%, p = 0.040). Patients with high NLR change (>1.61) showed worse OS and LRPFS than those with low NLR change (2-year OS: 26.0% vs. 59.0%, p < 0.001; 2-year LRPFS: 6.8% vs. 31.8%, p = 0.004). The planning target volume (hazard ration [HR] = 2.05, p = 0.028) and NLR change (HR = 3.17, p = 0.025) were the significant factors for OS in the multivariate analysis. Conclusion NLR change after CCRT was associated with poor prognosis of survival in patients with locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased treatment failure risk.

Background Several studies have suggested risk factors for poor survival in stage IB non–small-cell lung cancer (NSCLC) patients. However, these factors are not definite indicators of adjuvant chemotherapy for stage IB cancer, and most of them can be used to consider adjuvant chemotherapy. We aimed to determine the clinicopathologic factors and assess whether c-MET is a prognostic factor in stage IB NSCLC patients who have undergone surgery. Additionally, we determined the relevance of the factors and the recurrence pattern in these patients. Patients and Methods This study included 115 patients who underwent resection of pathologic stage IB NSCLC between January 2005 and December 2013. We retrospectively reviewed the clinicopathologic data and performed immunohistochemical analysis for c-MET. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated according to clinicopathologic factors and c-MET expression. Results Lymphovascular invasion (LVI) and c-MET overexpression were significantly associated with poor RFS. A large tumor with visceral pleural invasion (VPI) or LVI, moderate/poor differentiation with LVI, and VPI with LVI were negative prognostic factors for RFS and CSS. c-MET overexpression with a large tumor, VPI, or LVI was an independent prognostic factor for poor RFS and CSS, and LVI was a significant factor for distant recurrence. Conclusion LVI and c-MET overexpression might be associated with poor prognosis in stage IB NSCLC patients. Additionally, survival might be poor in stage IB patients with multiple pathologic risk factors. Moreover, there is a high possibility of distant recurrence in patients with LVI.

Purpose We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). Materials and methods A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. Results After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). Conclusion This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

The aim of this study was to analyze tumor control and clinical outcomes of patients with uterine cervical cancer treated by chemoradiotherapy according to pelvic lymph node (PLN) positivity and boost irradiation to PLN and to determine toxicities associated with boost irradiation. We retrospectively reviewed patients with uterine cervical cancer treated with chemoradiotherapy between March 2000 and April 2015. Clinical characteristics, failure pattern, and survival outcomes of patients with or without PLN metastasis and those with or without boost irradiation were analyzed. A total of 80 cases were PLN-negative and 46 were PLN-positive. A total of 11 patients underwent PLN boost irradiation. The 2-year and 5-year overall survival (OS) rates showed significant difference between the PLN-positive and PLN-negative groups (P = .010). The 2-year and 5-year progression-free survival (PFS) rates showed significant difference between the 2 groups (P = .032). The 2-year and 5-year OS rates of the no-boost irradiation group were 82.9% and 58.3%, respectively, whereas all patients in the boost irradiation group were alive at the time of analysis (P = .065). There was no recurrence in the boost irradiation group. The difference in PFS was significant between the boost and the no-boost irradiation groups (P = .023). The 2-year and 5-year pelvic-recurrence free survival (PRFS) did not show significant difference but the tendency of increased risk of pelvic recurrence in no-boost group (boost vs no-boost; 81.9% and 70.2% vs 100% and 100% in 2-year and 5-year PRFS, respectively, P = .156). Boost irradiation to PLN could improve locoregional control especially in large pelvic LN (≥1.5 cm). Our results showed that only 1 acute and late toxicity of higher than grade 3 occurred. PLN metastasis was significant prognostic factor in cervix cancer treated by chemoradiotherapy. In the boost irradiation group, there was no recurrence or death with significantly better PFS. Boost irradiation to PLN is expected to improve locoregional control, but further follow-up and assessment are needed.

The efficacy of tyrosine kinase inhibitors (TKIs) with and without radiotherapy (RT) has not been determined in patients with brain metastases from epidermal growth factor receptor-mutant TKI naive non-small cell lung cancer (NSCLC). Between 2008 and 2016, 586 patients were diagnosed with NSCLC and treated with TKIs at a hospital in Seoul, South Korea; 81 of these patients met the eligibility criteria for our study. Outcomes analyzed included intracranial progression (ICP), neurological death, and overall survival (OS). The 2-year cumulative incidence of ICP was 36.5% in the TKI plus RT group and 62.2% in the TKI alone group (P = 0.006). The chronological pattern analysis indicated that 64.3% of ICP developed within 12 months of the start of TKI treatment in the TKI alone group. The multivariate analysis revealed that treatment group (P = 0.003) and duration of TKI treatment ≤ 12 months (P

Background Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure to evaluate suspicious lymph node involvement of lung cancer because computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT (PET-CT) have limitations in their sensitivity and specificity. There are a number of benign causes of false positive lymph node such as anthracosis or anthracofibrosis, pneumoconiosis, old or active tuberculosis, interstitial lung disease, and other infectious conditions including pneumonia. The purpose of this study was to evaluate possible causes of false positive lymph node detected in chest CT or PET-CT. Methods Two hundred forty-seven patients who were initially diagnosed with lung cancer between May 2009 and December 2012, and underwent EBUS-TBNA to confirm suspicious lymph node involvement by chest CT or PET-CT were analyzed for the study. Results Of 247 cases, EBUS-TBNA confirmed malignancy in at least one lymph node in 189. The remaining 58 patients whose EBUS-TBNA results were negative were analyzed. Age ≥65, squamous cell carcinoma as the histologic type, and pneumoconiosis were related with false-positive lymph node involvement on imaging studies such as chest CT and PET-CT. Conclusion These findings suggest that lung cancer staging should be done more carefully when a patient has clinically benign lymph node characteristics including older age, squamous cell carcinoma, and benign lung conditions.

Background Recent studies demonstrated that miR-137 is downregulated in various tumors, and that it functions as a tumor suppressor. miR-137 could be silenced by its aberrant promoter hypermethylation. The purpose of this study was to investigate the significance of MIR137 promoter methylation on its expression in lung cancer. Methods Lung cancer cell lines were treated with either a DNA methyltransferase inhibitor (5-azacytidine, AZA) and/or an HDAC inhibitor (trichostatin A, TSA) to determine whether miR-137 expression was reactivated. Paired lung tumor and adjacent non-tumor lung tissues were obtained ( n =50). Quantitative methylation-specific PCR and bisulfite sequencing were used to analyze the methylation status of MIR137 , and real-time RT-PCR was performed to analyze miR-137 expression. Results miR-137 was reactivated by treatment with either AZA and/or TSA in lung cancer cell lines. Methylation-specific PCR showed increased MIR137 promoter methylation in lung tumors compared with adjacent non-tumor tissues, which was further validated by bisulfite sequencing. The expression of miR-137 was downregulated significantly in lung tumors, which was correlated with level of MIR137 promoter methylation inversely. Conclusions miR-137 downregulation was related to its promoter hypermethylation in lung cancer. Further studies are needed to assess its value as a prognostic factor and potential therapeutic applications in lung cancer.

The purpose of this study is to evaluate the clinical usefulness of modulated arc (mARC) treatment techniques. The mARC treatment plans of the non-small cell lung cancer (NSCLC) patients were performed in order to verify the clinical usefulness of mARC. A pre study was conducted to find the most competent plan condition of mARC treatment and the usefulness of mARC treatment plan was evaluated by comparing it with the other Arc treatment plans such as Tomotherapy and RapidArc. In the case of mARC, the optimal condition for the mARC plan was determined by comparing the dosimetric performance of the mARC plans with the use of various parameters. The various parameters includes the photon energies (6 MV, 10 MV), optimization point angle (6{\deg}-10{\deg} intervals), and total segment number (36-59 segment). The best dosimetric performance of mARC was observed at 10 MV photon energy and the point angle 6 degree, and 59 segments. The each treatment plans of three different techniques were compared with the following parameters: conformity index (CI), homogeneity index (HI), target coverage, dose in the OARs, monitor units (MU), beam on time and the normal tissue complication probability (NTCP). As a result, all three different treatment techniques show the similar target coverage. The mARC results the lowest V20 and MU per fraction compared with both RapidArc and Tomotherapy plan. The mARC plan reduces the beam on time as well. Therefore, the results of this study provided a satisfactory result which mARC technique is considered as a useful clinical technique for radiation treatment., Comment: 11 pages, 4 figures

Purpose To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy. Materials and Methods From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy). Results Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last follow-up, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival. Conclusion Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

Purpose We examined clinical and dosimetric factors as predictors of symptomatic radiation pneumonitis (RP) in lung cancer patients and evaluated the relationship between interstitial lung changes in the pre-radiotherapy (RT) computed tomography (CT) and symptomatic RP. Materials and Methods Medical records and dose volume histogram data of 60 lung cancer patients from August 2005 to July 2006 were analyzed. All patients were treated with three dimensional (3D) conformal RT of median 56.9 Gy. We assessed the association of symptomatic RP with clinical and dosimetric factors. Results With a median follow-up of 15.5 months (range, 6.1 to 40.9 months), Radiation Therapy Oncology Group grade ≥ 2 RP was observed in 14 patients (23.3%). Five patients (8.3%) died from RP. The interstitial changes in the pre-RT chest CT, mean lung dose (MLD), and V30 significantly predicted RP in multivariable analysis (p=0.009, p < 0.001, and p < 0.001, respectively). MLD, V20, V30, and normal tissue complication probability normal tissue complication probability (NTCP) were associated with the RP grade but less so for grade 5 RP. The risk of RP grade ≥ 2, ≥ 3, or ≥ 4 was higher in the patients with interstitial lung change (grade 2, 15.6% to 46.7%, p=0.03; grade 3, 4.4% to 40%, p=0.002; grade 4, 4.4% to 33.3%, p=0.008). Four of the grade 5 RP patients had diffuse interstitial change in pre-RT CT and received chemoradiotherapy. Conclusion Our study identified diffuse interstitial disease as a significant clinical risk for RP, particularly fatal RP. We showed the usefulness of MLD, V20, V30, and NTCP in predicting the incidence and severity of RP.