Prophylactic Effect of Clarithromycin on Radiation Pneumonitis in IMRT for Lung Cancer.

BACKGROUND/AIM: To evaluate the association between prophylactic administration of clarithromycin (CAM) and the development of radiation pneumonitis (RP) in patients treated with intensity modulated radiation therapy (IMRT) for lung cancer. PATIENTS AND METHODS: A total of 89 patients who underwent definitive or salvage IMRT for lung cancer were retrospectively evaluated. The median total and daily doses were 60 Gy and 2 Gy, respectively. A total of 39 patients (44%) received CAM for a median of three months after the start of IMRT. The relationship between the development of RP and certain clinical factors was analyzed. RESULTS: RP of Grade ≥2 was recognized in 10 (11%) patients; Grade 2 in six patients and Grade 3 in four patients. The incidence of Grade ≥2 RP was 3% (1/39) in patients treated with CAM, which was significantly lower than that of 18% (9/50) in patients without CAM. The median lung V20 and V5 in the 10 patients with RP Grade ≥2 were 24% and 46%, respectively, compared with 18% and 37% in the 79 patients with RP Grade 0-1, and the differences were significant. Durvalumab administration after IMRT was also a significant factor for RP Grade ≥2. CONCLUSION: Prophylactic administration of CAM may reduce Grade ≥2 RP in patients treated with IMRT for lung cancer. Therefore, further clinical trials are warranted.

Retrospective analysis of prognosis using the Gynecology Oncology Group score of stage IB-IIA node negative uterine cervical cancer after radical hysterectomy and trachelectomy.

There is currently controversy regarding the criteria for low and intermediate risk of cervical cancer (CC) after surgery. In the present study, the Gynecology Oncology Group (GOG) score was used to detect intermediate risk. Adjuvant radiotherapy was applied in the case of a GOG score >120. The present study aimed to evaluate the validity of the recurrence risk classification using the GOG score for stage IB-IIA node-negative CC. All cases of stage IB-IIA node-negative CC who underwent radical surgery between February 2007 and December 2015 were retrospectively reviewed. The GOG scores were determined from clinical and pathological findings and accordingly, subjects were divided into 4 groups: A, ≤40; B, >40 and ≤70; C, >70 and ≤120; and D, >120. Overall survival (OS) and recurrence-free survival (RFS) curves were generated using the Kaplan-Meier method. The log-rank test produced an estimated P-value by comparing the OS and RFS of group A (low-score group) with those of others. The present study included 61 patients (mean age, 47.82 years; age range, 22-76 years) and the median follow-up was 79 (39-149) months. Of these, 60 patients were observed for at least 60 months. During the follow-up period, the OS and RFS rates of group C were 94.7 and 84.2%, respectively, while those of group D were 100 and 91.7%, respectively; the OS and RFS of groups A and B were 100%. Log-rank tests for all OS and RFS indicated no significant differences compared to group A. It was indicated that a GOG score ≤70 does not require adjuvant therapy; however, a GOG score >70 requires consideration of adjuvant therapy based on the risk factors which constitute the score.

Intensity-Modulated Radiotherapy with Regional Hyperthermia for High-Risk Localized Prostate Carcinoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of adding regional hyperthermia to intensity-modulated radiotherapy (IMRT) plus neoadjuvant androgen deprivation therapy (ADT) for high-risk localized prostate carcinoma. METHODS: Data from 121 consecutive patients with high-risk prostate carcinoma who were treated with IMRT were retrospectively analyzed. The total planned dose of IMRT was 76 Gy in 38 fractions for all patients; hyperthermia was used in 70 of 121 patients. Intra-rectal temperatures at the prostate level were measured to evaluate thermal dose. RESULTS: Median number of heating sessions was five and the median total thermal dose of CEM43T90 was 7.5 min. Median follow-up duration was 64 months. Addition of hyperthermia to IMRT predicted better clinical relapse-free survival. Higher thermal dose with CEM43T90 (>7 min) predicted improved biochemical disease-free survival. The occurrence of acute and delayed toxicity ≥Grade 2 was not significantly different between patients with or without hyperthermia. CONCLUSIONS: IMRT plus regional hyperthermia represents a promising approach with acceptable toxicity for high-risk localized prostate carcinoma. Further studies are needed to verify the efficacy of this combined treatment.

Salvage Re-irradiation with Intensity-modulated Radiotherapy, Chemotherapy Combined with Hyperthermia for Local Recurrence of Nasopharyngeal Carcinoma After Chemoradiotherapy.

A sufficient dose of radiation is difficult to administer in re-irradiation for local recurrence of cancer after radiotherapy because of the dose limitation to organs at risk. Re-irradiation cases also include radioresistant tumors that are difficult to control locally, and their prognosis is poor in general. The effect of re-irradiation using intensity-modulated radiotherapy (IMRT) has recently been reported to significantly reduce the dose to organs at risk, and the efficacy of hyperthermia has been reported for radioresistant tumors. We report a case of local recurrence after concurrent chemoradiotherapy treated with salvage re-irradiation using IMRT and chemotherapy combined with hyperthermia in a patient with nasopharyngeal carcinoma, and include a discussion of the literature.

Optimization of the Clinical Setting Using Numerical Simulations of the Electromagnetic Field in an Obese Patient Model for Deep Regional Hyperthermia of an 8 MHz Radiofrequency Capacitively Coupled Device in the Pelvis.

Background: The purpose of this study was to evaluate the effectiveness of the clinical setting for deep regional hyperthermia of an 8 MHz radiofrequency (RF) capacitively coupled device in the pelvis by using numerical simulations of the electromagnetic field. Methods: A three-dimensional patient model of cervical cancer of the uterus in an obese patient was reconstructed with computed tomography data. The specific absorption rate (SAR) and temperature distributions among the various heating settings were evaluated using numerical simulations. Results: The averaged SAR value of the deep target tumor was similar between with or without overlay boluses (OBs), and that of the subcutaneous fat (SF) at the edges of cooling boluses with OBs was lower than that of the SF without OBs. The use of OBs reduced the overheating of the SF. The 0.5% salt solution in the OB produced the least overheated areas outside the deep target tumor compared with the other concentrations. The insertion of the intergluteal cleft (IGC) bolus could improve the temperature concentration of the deep target tumor. Conclusions: The use of OBs and the salt solution concentration in the OB were important to optimize the temperature distribution. IGC bolus might contribute to temperature optimization. Further studies with individualized numerical simulations in each patient are expected.

Pembrolizumab-induced Radiation Recall Pneumonitis After the Resolution of Typical Asymptomatic Radiation Pneumonitis.

Radiation recall pneumonitis is a phenomenon in which a recall-triggering drug induces an acute inflammatory reaction in the lungs, corresponding to a previously irradiated area. Radiation recall reactions have been reported to occur following treatments with various cytotoxic anticancer agents and molecular-targeting drugs; however, only a few reports have described immune checkpoint inhibitor-induced radiation recall pneumonitis. We report a case of radiation recall pneumonitis induced by pembrolizumab in a patient with the postoperative local recurrence of non-small cell lung cancer. This case demonstrated that pembrolizumab might cause severe radiation recall pneumonitis, even after typical radiation pneumonitis has been resolved.

Pediatric nasopharyngeal cancer with repeated oligometastases involving the bone, liver and distant lymph nodes who achieved cure after radiotherapy.

Systemic chemotherapy is a standard treatment for Stage IVc nasopharyngeal carcinoma (NPC). Stage IVc NPC patients with oligometastases have a better prognosis, and local therapy has an important role in further development of the disease. However, the efficacy of local therapy to the metastases in patients with multiple-site and/or multiple-organ metastases is limited due to the aggressive behavior of the tumor. We report a NPC case in a pediatric patient with repeated oligometastases involving the bone, liver and distant lymph nodes who achieved 10-year disease free status after initial chemotherapy and radiotherapy to all the metastases. This very rare case demonstrated that radiotherapy to oligometastatic lesions have a potential to cure repeated oligometastases which involved multiple-organ metastases in a pediatric NPC with stage IVc.

Early volume reduction of the hippocampus after whole-brain radiation therapy: an automated brain structure segmentation study.

PURPOSE: To assess atrophy differences among brain regions and time-dependent changes after whole-brain radiation therapy (WBRT). MATERIALS AND METHODS: Twenty patients with lung cancer who underwent both WBRT and chemotherapy (WBRT group) and 18 patients with lung cancer who underwent only chemotherapy (control group) were recruited. Three-dimensional T1WI were analyzed to calculate volume reduction ratio after WBRT in various brain structures. The volume reduction ratio of the hippocampus was compared among following 3 periods: 0-3, 4-7, and 8-11 months after WBRT. RESULTS: The volume reduction ratio of the hippocampus was significantly higher in the WBRT group than in the control group (p < 0.05). In WBRT group, the volume reduction ratio of the hippocampus was significantly higher than that of the cortex and white matter (p < 0.05). There were significant differences in the volume reduction ratio between of 0-3 months and that of 4-7 months (p = 0.02) and between 4-7 months and that of 8-11 months (p = 0.01). CONCLUSION: The hippocampus is more vulnerable to the radiation compared with other brain regions and may become atrophic even in the early stage after WBRT.

Predictive gamma passing rate for three-dimensional dose verification with finite detector elements via improved dose uncertainty potential accumulation model.

PURPOSE: We aim to develop a method to predict the gamma passing rate (GPR) of a three-dimensional (3D) dose distribution measured by the Delta4 detector system using the dose uncertainty potential (DUP) accumulation model. METHODS: Sixty head-and-neck intensity-modulated radiation therapy (IMRT) treatment plans were created in the XiO treatment planning system. All plans were created using nine step-and-shoot beams of the ONCOR linear accelerator. Verification plans were created and measured by the Delta4 system. The planar DUP (pDUP) manifesting on a field edge was generated from the segmental aperture shape with a Gaussian folding on the beam's-eye view. The DUP at each voxel ( u ) was calculated by projecting the pDUP on the Delta4 phantom with its attenuation considered. The learning model (LM), an average GPR as a function of the DUP, was approximated by an exponential function a GPR u = e - q u to compensate for the low statistics of the learning data due to a finite number of the detectors. The coefficient q was optimized to ensure that the difference between the measured and predicted GPRs ( d GPR ) was minimized. The standard deviation (SD) of the d GPR was evaluated for the optimized LM. RESULTS: It was confirmed that the coefficient q was larger for tighter tolerance. This result corresponds to the expectation that the attenuation of the a GPR u will be large for tighter tolerance. The p GPR and m GPR were observed to be proportional for all tolerances investigated. The SD of d GPR was 2.3, 4.1, and 6.7% for tolerances of 3%/3 mm, 3%/2 mm, 2%/2 mm, respectively. CONCLUSION: The DUP-based predicting method of the GPR was extended to 3D by introducing DUP attenuation and an optimized analytical LM to compensate for the low statistics of the learning data due to a finite number of detector elements. The precision of the predicted GPR is expected to be improved by improving the LM and by involving other metrics.

Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer.

BACKGROUND: Consolidation treatment with an anti-PD-L1 antibody, durvalumab, following concurrent chemo-radiotherapy (cCRT) has become a new standard of care for locally advanced non-small cell lung cancer (NSCLC). The rationale of PD-L1 blockade after cCRT is based on preclinical evidence suggesting that chemotherapy and radiotherapy up-regulate tumoural PD-L1 expression, which has not been shown in clinical studies. METHODS: To examine alteration in tumoural PD-L1 expression (tumour proportion score, TPS) and density of stromal CD8-positive tumour-infiltrating lymphocytes (CD8 + TILs) after cCRT, paired NSCLC samples obtained before and after cCRT were reviewed in comparison with those obtained before and after drug therapy. RESULTS: PD-L1 expression was significantly up-regulated after cCRT (median TPS, 1.0 at baseline versus 48.0 after cCRT; P < 0.001), but not after drug therapy. There was no significant correlation between baseline TPS and post-cCRT TPS. CD8 + TIL density was significantly increased after cCRT (median, 10.6 versus 39.1; P < 0.001), and higher post-cCRT CD8 + TIL density was associated with a higher pathologic response and with a favourable survival (P = 0.019). CONCLUSION: Tumoural PD-L1 expression was up-regulated after cCRT, which provides pathologic rationale for PD-L1 blockade following cCRT to improve prognosis. Stromal CD8 + TIL density was also increased after cCRT, and higher post-cCRT CD8 + TIL density was a favourable prognostic indicator.

Predictive gamma passing rate by dose uncertainty potential accumulation model.

PURPOSE: Intensity-modulated radiation therapy (IMRT) utilizes many small fields for producing a uniform dose distribution. Therefore, there are many field junctions in the target region, and resulting dose uncertainties are accumulated. However, such accumulation of the dose uncertainty has not been implemented in the current practice of IMRT dose verification. The purpose of this study is to develop a method to predict the gamma passing rate (GPR) using a dose uncertainty accumulation model. METHODS: Thirty-three intensity-modulated (IM) beams for head-and-neck cases with step-and-shoot techniques were used in this study. The treatment plan was created using the XiO treatment planning system (TPS). The IM beam was produced by the ONCOR Impression Plus linear accelerator. MapCHECK was used to measure the dose distribution. The distribution of a dose uncertainty potential (DUP) was generated by in-house software that accumulated field shapes weighted by a segmental monitor unit, followed by Gaussian folding. The width of the Gaussian was determined from the width of the lateral penumbra. The dose difference between the calculated and measured doses was compared with the estimated DUP at each point. The GPR of each beam was predicted for 2%/2-mm, 3%/2-mm, and 3%/3-mm tolerances by its own DUP histogram and a GPR-vs-DUP correlation of other beams using the leave-one-out cross-validation method. The predicted GPR was compared with the measured GPR to evaluate the performance of this prediction method. The criteria for the predicted GPR corresponding to a measured GPR ≥ 90% were estimated to examine the feasibility of estimating the measured GPR by this GPR prediction method. RESULTS: The DUP was confirmed to have proportionality to the standard deviation (SD) of the dose difference. The SDs of the difference between the measured and predicted GPRs were 3.1, 1.7, and 1.4% for 2%/2-mm, 3%/2-mm, and 3%/3-mm tolerances, respectively. The criteria of the predicted GPR corresponding to the measured GPR ≥ 90% were 94.1 and 95.0% with confidence levels of 99 and 99.9%, respectively. CONCLUSION: In this study, we confirmed the good proportionality between the dose difference and the estimated DUP. The results showed a feasibility to predict the dose difference from DUP as estimated by a DUP accumulation model. The predicted GPR developed in this study showed good accuracy for planar dose distributions of head and neck IMRT. The prediction method developed in this study is considered to be feasible as a substitute for the current practice of measurement-based verification of the dose distribution with gamma analysis.

The usefulness of mobile insulator sheets for the optimisation of deep heating area for regional hyperthermia using a capacitively coupled heating method: phantom, simulation and clinical prospective studies.

PURPOSE: To evaluate the feasibility and efficacy of deep regional hyperthermia with the use of mobile insulator sheets in a capacitively coupled heating device. MATERIALS AND METHODS: The heat was applied using an 8-MHz radiofrequency-capacitive device. The insulator sheet was inserted between the regular bolus and cooled overlay bolus in each of upper and lower side of the electrode. Several settings using the insulator sheets were investigated in an experimental study using an agar phantom to evaluate the temperature distributions. The specific absorption rate (SAR) distributions in several organs were also computed for the three-dimensional patient model. In a clinical prospective study, a total of five heating sessions were scheduled for the pelvic tumours, to assess the thermal parameters. The conventional setting was used during the first, third and fifth treatment sessions, and insulator sheets were used during the second and fourth treatment sessions. RESULTS: In the phantom study, the higher heating area improved towards the centre when the mobile insulator sheets were used. The subcutaneous fat/target ratios for the averaged SARs in the setting with the mobile insulator (median, 2.5) were significantly improved compared with those in the conventional setting (median, 3.4). In the clinical study, the thermal dose parameters of CEM43°CT90 in the sessions with the mobile insulator sheets (median, 1.9 min) were significantly better than those in the sessions using a conventional setting (median, 1.0 min). CONCLUSIONS: Our novel heating method using mobile insulator sheets was thus found to improve the thermal dose parameters. Further investigations are expected.

Salvage radiotherapy for second oligo-recurrence in patients with breast cancer.

A new concept designated 'oligo-recurrence (OR)' has been proposed, which indicates one to several distant metastases/recurrences in one or more organs, which can be treated with local therapy, after the primary site of the cancer has been controlled. The purpose of this study was to assess the efficacy and toxicity of salvage radiotherapy (RT) for the second OR of breast cancer. The second OR was defined as once-salvaged patients with OR who had a second failure that was also detected as the state of OR. Twenty-one patients with second OR were treated with salvage RT and were retrospectively analyzed. The sites of the second OR were locoregional recurrence in 7 patients and distant metastasis in 14 patients. Salvage RT was performed at a median total dose of 60 Gy. Nineteen (90%) patients had an objective response. The median overall survival and progression-free survival (PFS) times were 41 and 24 months after salvage RT for the second OR, respectively. The 3-year local (in-field) control (LC) rates were 93%. The toxicities were mild; acute toxicities ≥Grade 3 were seen in one patient with Grade 3 dermatitis, and no late toxicity ≥Grade 2 was observed. In conclusion, salvage RT for the second OR was able to achieve a better LC rate and longer PFS time without inducing severe toxicity, and therefore may be a potentially effective modality for inducing long-term survival in select patients.

Relationships between thermal dose parameters and the efficacy of definitive chemoradiotherapy plus regional hyperthermia in the treatment of locally advanced cervical cancer: data from a multicentre randomised clinical trial.

PURPOSE: To evaluate the contribution of the thermal dose parameters during regional hyperthermia (HT) treatment to the clinical outcomes in patients with cervical carcinoma (CC) who received chemoradiotherapy (CRT) plus HT. MATERIALS AND METHODS: Data from a multicentre randomised clinical trial of concurrent CRT + HT vs. CRT alone were used to evaluate the efficacy and safety of this combination therapy in the CC patients. The intrarectal temperatures of patients undergoing HT were recorded. The complete thermal data of 47 (92%) of the 51 patients in the CRT + HT group were available for the thermal analysis. Thus, 47 patients who received CRT + HT were included in the present study. RESULTS: Among the patients who received CRT + HT, a higher CEM43T90 (≥1 min) value (a thermal dose parameter) was significantly associated with better local relapse-free survival in both univariate (p = 0.024) and multivariate (p = 0.0097) analyses. The disease-free survival of the patients with higher CEM43T90 (≥1 min) values tended to be better in comparison to patients with lower CEM43T90 (<1 min) value (p = 0.071). A complete response tended to be associated with the CEM43T90 (p = 0.056). Disease-free survival, local relapse-free survival and complete response rate for patients with higher CEM43T90 (≥1) were significantly better than those for patients with CRT alone (p = 0.036, p = 0.036 and p = 0.048). CONCLUSIONS: Dose-effect relationships between thermal dose parameters and clinical outcomes were confirmed in the CC patients treated with a combination of CRT + HT. This study also confirmed that HT with lower CEM43T90 is insufficient to achieve a significant hyperthermic sensitisation to CRT.

Salvage Radiotherapy for Solitary Metachronous Bone Metastasis in Patients with Breast Cancer.

AIM: We assessed the efficacy and toxicity of salvage radiotherapy for solitary metachronous bone metastasis (SMBM) in patients with breast cancer. PATIENTS AND METHODS: We retrospectively analyzed 17 patients with SMBM who were treated with salvage radiotherapy. First failure was detected as SMBM in all patients. Salvage radiotherapy using three-dimensional treatment planning was performed at a median total dose of 50 Gy. Median daily dose was 2.0 Gy. RESULTS: Median follow-up was 40 months. Local recurrence of SMBM was noted in only two patients. The 3-year overall survival, progression-free survival, and local control rates were 93%, 51%, and 85%, respectively. Median overall and progression-free survival were 74 and 30 months, respectively. Toxicities were mild, and bone fractures were not observed. CONCLUSION: Salvage radiotherapy for SMBM was able to achieve higher local control rates without severe toxicity, as well as to provide longer progression-free survival; therefore, this may be an effective modality.

Cardiac and respiratory effects of deep regional hyperthermia using an 8 MHz radiofrequency-capacitive device on patients with cancer.

PURPOSE: Hyperthermia (HT), an adjuvant therapy for variable cancers, may cause physiological changes in the patients, which may lead to cardiovascular problems. Among various HT treatments, the physiological effects of deep regional HT are still unclear. We examined the physiological alterations throughout deep regional HT to improve the HT safety. MATERIALS AND METHODS: Thirty-one patients (age: 61 ± 12 years) with cancer received HT in the thoracic or upper abdominal regions using an 8-MHz radiofrequency-capacitive-device for 50 min. Rectal temperature (Trec), systolic and diastolic blood pressures (SBP and DBP), pulse rate (PR), respiratory rate (RR), percutaneous oxygen saturation (SpO2) and sweating volume were evaluated throughout HT. RESULTS: At 50 min after starting HT, Trec, PR and RR were significantly increased compared with the baseline values (Trec: 38.2 ± 1.4 vs. 36.3 ± 0.8 °C, p < 0.001, PR: 104 ± 15 vs. 85 ± 16 bpm, p < 0.05, RR: 23 ± 3 vs. 21 ± 3/min, p < 0.05). Although the average SBP and DBP were both stable during HT in a recumbent position, these values dropped significantly in a standing position (SBP: 113 ± 16 vs. 127 ± 18 mmHg, p < 0.001, DBP: 70 ± 12 vs. 75 ± 13 mmHg, p < 0.01). The total amount of sweating was 356 ± 173 g/m2 on average. CONCLUSIONS: Deep regional HT increased the deep body temperature and resulted in an increase of sweating with peripheral vasodilatation. Consequently, a significant reduction in BP would be induced on standing after HT. Careful attention is needed for patients receiving HT, especially when standing after HT.

Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy for glioblastoma.

The purpose of this study was to evaluate the feasibility and efficacy of radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma. Twenty-four patients with glioblastoma were treated with the combined therapy, which was RT using IMRT boosts after HBO with chemotherapy, and were retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the surrounding edema, including an additional 1.5-2.0 cm. The IMRT boost doses were then continuously delivered to the GTV plus 5 mm (28 Gy/8 fr) and the surrounding edema (16 Gy/8 fr). Each IMRT boost session was performed immediately after HBO to achieve radiosensitization. The planned RT dose was completed in all patients, while HBO therapy was terminated in one patient (4%) due to Grade 2 aural pain. The toxicities were mild, no non-hematological toxicity of Grade 3-5 was observed. The 2-year overall survival (OS) and progression-free survival rates in all patients were 46.5% and 35.4%, respectively. The median OS time was 22.1 months. In conclusion, the combined therapy of RT using IMRT boosts after HBO with chemotherapy was a feasible and promising treatment modality for patients with glioblastoma. The results justify further evaluation to clarify the benefits of this therapy.

A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer.

PURPOSE: To evaluate the effectiveness of whole-pelvic hyperthermia (HT) added to standard chemoradiotherapy (CRT) in locally advanced cervical cancer (CC), by investigating the clinical response and survival of patients treated with cisplatin-based CRT vs. CRT with HT (CRT + HT). MATERIALS AND METHODS: This study was conducted at five hospitals in Japan between September 2001 and March 2015 in patients with the International Federation of Gynecology and Obstetrics stage IB (bulky)-IVA CC undergoing definitive CRT. After giving a written informed consent, patients were randomly allocated to two treatment groups: CRT and CRT + HT group. Overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), complete response (CR) rate and tolerability were evaluated. RESULTS: In total, 101 patients were treated. Patient characteristics, total dose of cisplatin and radiotherapy were similar for both groups. Although not statistically significant, the 5-year OS, DFS and LRFS in the CRT + HT group (77.8%, 70.8% and 80.1%, respectively) were better than those in the CRT group (64.8%, 60.6% and 71.0%, respectively). CR was significantly more likely to be achieved in patients in the CRT + HT group than in the CRT group (88% vs. 77.6%; adjusted odds ratio, 3.993; 95% confidence interval, 1.018-15.67; p = .047). CRT + HT was well tolerated and caused no additional acute or long-term toxicity compared with CRT alone. CONCLUSIONS: HT combined with CRT improved the CR rate of CRT in patients with locally advanced CC, however, could not improve survival outcomes. Further studies in larger samples are warranted.

Conversion to Neuroendocrine Carcinoma from Squamous Cell Carcinoma of the Esophagus After Definitive Chemoradiotherapy.

BACKGROUND/AIM: Neuroendocrine carcinoma (NEC) of the esophagus is rare and aggressive. We herein report a case of a patient who showed NEC conversion from squamous cell carcinoma (SCC) of the esophagus in the recurrent lesion after definitive chemoradiotherapy. CASE REPORT: The patient was a 57-year-old Japanese male with mid-thoracic esophageal carcinoma diagnosed as SCC with invasion of the submucosal layer. After definitive chemoradiotherapy, the esophageal tumor completely disappeared. Two months later, local recurrence was recognized at the same location and salvage surgery was performed. An immunohistochemical examination of the resected specimen revealed that most of the recurrent tumor had neuroendocrine (NE) differentiation, although a retrospective review of the initial biopsy specimen showed no involvement of NE differentiation. CONCLUSION: This case is significant not only in bringing attention to the possibility of NEC conversion from SCC after chemoradiotherapy, but also in discussing tumors originating in the esophagus.

Concurrent hyperfractionated chemoradiotherapy for head and neck squamous cell carcinoma: the prognostic impact of the overall treatment time and completion rates of chemotherapy.

The purpose of this study was to investigate whether the overall treatment time and completion rates of chemotherapy were predictive factors for the survival rates in patients with squamous cell carcinoma of the head and neck (SCCHN) who were treated with concurrent chemoradiotherapy (CCRT) using hyperfractionated radiotherapy (RT) and daily carboplatin. The number of intermission days of RT were as follows; 0 (n = 37), 1-5 (n = 8), 6-10 (n = 12) and ≥11 (n = 12), and the days of RT without carboplatin; 0 (n = 27), 1-5 (n = 13), 6-10 (n = 13) and ≥7 (n = 16). The overall treatment time (≤48 vs ≥49 days) was a significant prognostic factor for the local control, disease-free survival and overall survival rates. The completion rate of chemotherapy, as the number of days of RT without carboplatin, was not a significant factor affecting any of the survival rates. In discussion, the strengths of the present study contain that all the patients were treated with 72 Gy delivered as 1.2 Gy twice daily, and received concurrent chemotherapy comprising daily carboplatin as a radio-sensitizer. Based on the results, the completion rate of chemotherapy may have a lower impact on the local control rate in comparison with the overall treatment time. We believe that when a treatment interruption is needed because of the acute toxicities, hyperfractionated RT should be resumed as soon as possible independently while continuing the break of daily carboplatin. The overall treatment time influenced the clinical outcomes in SCCHN patients treated with hyperfractionated CCRT using carboplatin, while the impact of the completion rates of daily carboplatin was limited. Sixty-nine consecutive patients with SCCHN were initially treated with definitive CCRT and were retrospectively analyzed. All 69 patients were treated with CCRT using hyperfractionated RT of 72 Gy in 60 fractions and daily carboplatin (25 mg/m(2)). The patients treated with other chemotherapeutic regimens or induction chemotherapy were excluded. On the intermission days of the RT, carboplatin was not prescribed. After the intermission, CCRT using RT plus daily carboplatin or RT alone was resumed.