BACKGROUNDS: Since the recent development of molecular targeted drugs and immune checkpoint inhibitors has improved lung cancer treatment options and outcomes, supporting patients in balancing work and pharmacotherapy have become even more important in the field of lung cancer treatment. This study sought to identify the current status and roles of doctors in balancing work and treatment for lung cancer patients. METHODS: Patients and doctors were recruited to complete a web-based questionnaire survey by the Japan Lung Cancer Society. RESULTS: About 287 lung cancer patients and 381 doctors were included in the analysis. About 42.9% of patients responded that "there was no discussion" about their working conditions or work before the initiation of pharmacotherapy, while 22.6% responded that "there was an inquiry from a doctor/health care provider and a discussion that included the doctor was held." About 45.3% of patients took leave or resigned from work at the time of diagnosis. The most common reasons for patients to resign before or during pharmacotherapy were "poor physical condition due to side effects of treatment or illness" and "concern about causing problems in the workplace." To assist in balancing work and pharmacotherapy, patients desired "increased opportunities to consult about work" (36.9%) and "provision of treatment options with few adverse events" (28.9%). CONCLUSION: This study highlights the importance of doctor-initiated management of the balance between work and treatment for lung cancer patients. An important first step is for doctors themselves to take an interest in their patients' professions and initiate discussions of work-related topics with their patients.

The aim of the study was to evaluate inter-fractional dosimetric variations for high-dose rate breast brachytherapy using a strut-adjusted volume implant (SAVI). For the nine patients included, dosimetric constraints for treatment were as follows: for the planning target volume for evaluation (PTV_Eval), the volume receiving 90, 150 and 200% of the prescribed dose (V90%,150%,200%) should be >90%, ≤50 cm3 and ≤20 cm3, respectively; the dose covering 1 cm3 (D1cc) of the organs at risk should be ≤110% of the prescribed dose; and the air volume should be ≤10% of PTV_Eval. Differences in V90%,150%,200%, D1cc and air volume ($\Delta V$ and $\Delta D$) as inter-fractional dosimetric variations and SAVI displacements were measured with pretreatment and planning computed tomography (CT) images. Inter-fractional dosimetric variations were analyzed for correlations with the SAVI displacements. The patients were divided into two groups based on the distance of the SAVI from the surface skin to assess the relationship between the insertion position of the SAVI and dosimetric parameters. The median ΔV90%,150%,200% for the PTV_Eval in all patients was -0.3%, 0.2 cm3 and 0.2 cm3, respectively. The median (range) ΔD1cc for the chest wall and surface skin was -0.8% (-18.9 to 9.4%) and 0.3% (-7.6 to 5.3%), respectively. SAVI displacement did not correlate with inter-fractional dosimetric variations. In conclusion, the dose constraints were satisfied in most cases. However, there were inter-fractional dosimetric changes due to SAVI displacement.

Objective: To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy (ADT) in high-risk prostate cancer in three radiotherapy dose groups. Methods: Between 1998 and 2013, patients with high-risk prostate cancer underwent three-dimensional conformal radiotherapy or intensity-modulated radiotherapy of 66 Gy, 72 Gy, or 78 Gy with ADT. Prostate-specific antigen (PSA) relapse was defined using the Phoenix definition. PSA relapse-free survival (PRFS) was evaluated in each radiotherapy dose group. Moreover, high-risk patients were divided into H-1 (patients with multiple high-risk factors) and H-2 (patients with a single high-risk factor) as risk subgroups. Results: Two hundred and eighty-nine patients with a median follow-up period of 77.3 months were analyzed in this study. The median duration of ADT was 10.1 months. Age, Gleason score, T stage, and radiotherapy dose influenced PRFS with statistical significance both in univariate and multivariate analyses. The 4-year PRFS rates in Group-66 Gy, Group-72 Gy and Group-78 Gy were 72.7%, 81.6% and 90.3%, respectively. PRFS rates in the H-1 subgroup differed with statistical significance with an increasing radiotherapy dose having a more favorable PRFS, while PRFS rates in H-2 subgroup did not differ with increase in radiotherapy dose. Conclusion: Dose escalation for high-risk prostate cancer in combination with ADT improved PRFS. PRFS for patients in the H-1 subgroup was poor, but dose escalation in those patients was beneficial, while dose escalation in the H-2 subgroup was not proven to be effective for improving PRFS.

BACKGROUND: To determine the current practice of stereotactic irradiation (STI) for brain metastases in Japan by a questionnaire survey. METHODS: A questionnaire was distributed to 313 institutions performing STI with one of the following machines: Gamma Knife (GK), CyberKnife (CK), Novalis (Nov), or other linear accelerator (LINAC)-based systems (OLS). The participation was voluntary. RESULTS: There were 163 responding institutions. The total number of STI treatments between April 2013 and March 2014 was 10,684. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) were performed in 8624 (80.7%) and 2060 (19.3%) cases, respectively. Whole-brain radiation therapy (WBRT) was performed for a total of 3515 cases. For a case model of a 1.5-cm solitary brain metastasis in a non-eloquent area, the most common GTV-PTV margin was 2 mm (22 of 114 institutions), and an institutional standard fraction was 1 (75 of 114 institutions). The doses for the model case also varied from 13.0 to 26.0 Gy (Median 20 Gy) when converted to SRS (α/β = 10). A prescription point was at the PTV margin the most. The median dose constraints which were converted to SRS (α/β = 3) to organs at risk were 12.2, 12.7, and 13.7 Gy for optic nerves, cavernous sinus, and brainstem, respectively. CONCLUSIONS: STI for brain metastases in current practice varied significantly among institutions. These different strategies relied mostly on the type of treatment machine used. It is thus necessary to establish a common guideline to express dose prescriptions and plan qualities for different STI machines.

BACKGROUND/AIM: To evaluate long-term treatment outcomes of external beam radiotherapy for prostate cancer with a pretreatment prostate-specific antigen (PSA) level of more than 50 ng/ml and without evidence of lymph node or distant metastasis. PATIENTS AND METHODS: Definitive radiotherapy of 66 Gy or 72 Gy in combination with androgen deprivation therapy (ADT) was performed. PSA relapse-free survival (PRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), and overall survival (OS) were evaluated. The impact of prognostic factors on PRFS, DMFS, CSS, and OS was analyzed in univariate and multivariate analyses. RESULTS: One hundred twenty patients with a median follow-up period of 92.6 months were analyzed in this study. The median duration of ADT was 11.0 months. The 5- and 8-year PRFS rates in all patients were 65.1% and 48.5%, respectively. The 8-year DMFS, CSS, and OS rates in all patients were 84.0%, 93.4%, and 81.6%, respectively. Both in univariate and multivariate analyses, Gleason score (GS) and radiotherapy dose were significant prognostic factors (p=0.015 and 0.001). There was no significant difference between each prognostic factor in DMFS, CSS, and OS. CONCLUSION: We might have indicated the significance of definitive radiotherapy even for prostate cancer with PSA of more than 50 ng/ml and without evidence of metastasis.

AIM: To investigate the intrafraction movement of the esophagus using fiducial markers. BACKGROUND: Studies on intrafraction esophageal motion using the fiducial markers are scarce. MATERIALS AND METHODS: We retrospectively analyzed patients with clinical T1N0 esophageal cancer who had received fiducial markers at our hospital between July 2007 and December 2013. Real-Time Position Management System to track the patient's respiration was used, and each patient underwent three-dimensional computed tomography of the resting expiratory and inspiratory level. We used the center of the marker to calculate the distance between the expiratory and inspiratory breath-holds, which were measured with the radiotherapy treatment planning system in three directions: left-right (LR), superior-inferior (SI), and anterior-posterior (AP). The movements at each site were compared with the Kruskal-Wallis analysis and Wilcoxon rank sum test with a Bonferroni correction. RESULTS: A total of 101 patients with 201 fiducial markers were included. The upper, middle and lower thoracic positions had 40, 77, and 84 markers, respectively. The mean absolute magnitudes of the shifts (standard deviation) were 0.18 (0.19) cm, 0.68 (0.46) cm, and 0.24 (0.24) cm in the LR, SI, and AP directions, respectively. From the cumulative frequency distribution, we assumed that 0.35 cm LR, 0.8 cm SI, and 0.3 cm AP in the upper; 0.5 cm LR, 1.55 cm SI, and 0.55 cm AP in the middle; and 0.75 cm LR, 1.9 cm SI, and 0.95 cm AP in the lower thoracic esophagus covered 95% of the cases. CONCLUSIONS: The internal margin based on the site of esophagus was estimated.

PURPOSE: The aim of this study was to investigate the efficacy and safety of image-guided high-dose-rate (HDR) interstitial brachytherapy (ISBT) for reirradiation of locally recurrent uterine cervical cancer. METHODS AND MATERIALS: Between 2008 and 2015, patients receiving reirradiation using HDR-ISBT for local gross recurrence of uterine cervical cancer after definitive or postoperative radiotherapy were analyzed retrospectively. The prescription doses per fraction ranged 2.5-6.0 Gy, whereas the cumulative equivalent doses in 2 Gy fractions ranged 48.6-82.5 Gy. The effects of prognostic factors on the local control (LC), progression-free survival, and overall survival were analyzed, and late toxicity data were evaluated. RESULTS: Eighteen patients were included in the analysis, with a median followup of 18.1 months. A tumor response was obtained in all patients, with radiological and pathological complete remission seen in 12 (66.7%) patients. The 2-year LC, progression-free survival, and overall survival rates for all patients were 51.3%, 20.0%, and 60.8%, respectively. The hemoglobin level and maximum tumor diameter were shown to be statistically significant prognostic factors for LC (p = 0.028 and 0.009, respectively). Late ≥ Grade 2 adverse events were observed in 5 patients (27.8%). CONCLUSIONS: Image-guided HDR-ISBT for the reirradiation of locally recurrent uterine cervical cancer may play an important role for local tumor control in a subgroup of patients. However, the treatment indication must be weighed against the risk of higher-grade late toxicity.

PURPOSE: To determine the clinical efficacy of surgery followed by local brain radiotherapy (LBRT) for patients with a single brain metastasis, by comparing the results with those of postoperative whole brain radiotherapy (WBRT). METHODS: We performed a retrospective analysis to compare the survival rate, recurrence-free rates, and causes of death for single brain metastasis patients who underwent surgery followed by LBRT or WBRT in the 2010-2015 period. RESULTS: After their surgery, 22 and 32 patients were treated by LBRT and WBRT, respectively. The median survival times for these LBRT and WBRT groups were 18.3 months and 19.2 months, respectively (p = 0.356). The local recurrence-free rates were 81.2% at 1 year and 81.2% at 2 years after LBRT, and 63.8% at 1 year and 58.9% at 2 years after WBRT (p = 0.589). The distant brain recurrence-free rates were 42.5% at 1 year and 25.5% at 2 years after LBRT, and 69.8% at 1 year and 52.4% at 2 years after WBRT (p = 0.044). Distant brain recurrences were observed significantly more frequently in the LBRT group, but the rates of salvage treatment application and survival were not significantly different between the LBRT and WBRT groups. The probability of neurologic death was not significantly higher in the LBRT group compared with the WBRT group. CONCLUSIONS: Surgery followed by LBRT for single brain metastasis is not inferior to postoperative WBRT, because survival and the necessity of salvage treatment after LBRT were equivalent to those after WBRT.

PURPOSE: This study was designed to retrospectively analyze outcomes of high-dose-rate (HDR) brachytherapy, with or without external beam radiotherapy (EBRT), in patients with vaginal recurrence of endometrial carcinoma, and to identify factors prognostic of patient outcomes. MATERIAL AND METHODS: The medical records of all patients who underwent HDR brachytherapy for initial recurrence in the vagina of endometrial cancer after definitive surgery between 1992 and 2014 were retrospectively reviewed. All patients underwent either intracavitary brachytherapy (ICBT) or interstitial brachytherapy (ISBT) with or without EBRT. Late toxicity was graded using the EORTC (LENT/SOMA) scale, revised in 1995. RESULTS: Thirty-seven patients were identified. The median follow-up time was 48 months (range: 6-225 months). Of these 37 patients, 23 underwent ICBT, 14 underwent ISBT, and 26 underwent EBRT. Tumor size at first examination of initial relapse was significantly larger in the ISBT than in the ICBT group. The 4-year respective overall survival (OS), local control (LC), and progression-free survival (PFS) rates in the entire cohort were 81.0%, 77.9%, and 56.8%, respectively. The interval between diagnosis of first recurrence and radiotherapy (< 3 months, ≥ 3 months) was a significant predictor of LC and PFS. OS and LC rates did not differ significantly in the ICBT and ISBT groups. Two patients experienced grade 2 rectal bleeding, and four experienced grade 2 hematuria. No grade 3 or higher late complications were observed. CONCLUSIONS: Salvage HDR brachytherapy is an optimal for treating vaginal recurrence of endometrial carcinoma with acceptable morbidity. Early radiotherapy, including brachytherapy, should be considered for women who experience vaginal recurrence of endometrial cancer.

PURPOSE: The aim of this study was to report the clinical results of uterine cervical cancer patients treated by primary radiation therapy including brachytherapy, and investigate the role of interstitial brachytherapy (ISBT). MATERIAL AND METHODS: All consecutive uterine cervical cancer patients who were treated by primary radiation therapy were reviewed, and those who were treated by ISBT were further investigated for clinical outcomes and related toxicities. RESULTS: From December 2008 to October 2014, 209 consecutive uterine cervical cancer patients were treated with primary radiation therapy. Among them, 142 and 42 patients were treated by intracavitary and hybrid brachytherapy, respectively. Twenty-five patients (12%) were treated by high-dose-rate (HDR)-ISBT. Five patients with distant metastasis other than para-aortic lymph node were excluded, and 20 patients consisted of the analysis. Three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rate were 44.4%, 38.9%, and 87.8%, respectively. Distant metastasis was the most frequent site of first relapse after HDR-ISBT. One and four patients experienced grade 3 and 2 rectal bleeding, one grade 2 cystitis, and two grade 2 vaginal ulcer. CONCLUSIONS: Feasibility and favorable local control of interstitial brachytherapy for locally advanced cervical cancer was demonstrated through a single institutional experience with a small number of patients.

The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46-79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6-39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4-109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum.

PURPOSE: The kidney is a dose-limiting organ for upper abdominal radiotherapy. In this study, radiation-induced kidney injury represented by changes of creatinine clearance (Ccr) and renal parenchymal volume measured by computed tomography (CT) were evaluated by analysing dose-volume histograms (DVHs) in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL) treated with chemoradiotherapy. MATERIALS AND METHODS: Thirty-eight PGDLBCL patients (seventy-six kidneys) treated with chemoradiotherapy were included in this study. At least 4 years of follow-up was required for eligibility. Patients underwent (immuno-) chemotherapy followed by radiotherapy with approximately 40Gy to the whole stomach and perigastric lymph nodes. Ccr and CT were obtained at least annually. Changes of Ccr and renal parenchymal volume before and 4years after radiotherapy were compared using DVH parameters. RESULTS: Mean Ccr decreased significantly from 82.7mL/min (range, 39-124mL/min) before radiotherapy to 70.4mL/min (range, 35-109mL/min) (p=0.01) 4years after radiotherapy. Mean reduction of bilateral renal parenchymal volume was 12% (range, -5-37%) in the same time period. Ccr and renal parenchymal volume tended to lower over time more than 4years after radiotherapy. Concerning DVH analysis, V20Gy⩾26.6% and D30%⩾19Gy had a significant risk of bilateral renal atrophy of ⩾14% and reduction of the Ccr⩾20mL/min. CONCLUSION: This study revealed that there was a definite relationship between DVH, renal atrophy and Ccr reduction. V20Gy<26.6% and D30%<19Gy appeared to be safe dose constraints for a Ccr reduction of <20mL/min 4years after radiotherapy.

BACKGROUND: The aim of this study was to report the clinical results of salvage high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with cervical cancer with pelvic recurrence after hysterectomy. PATIENTS AND METHODS: When there was no indication for total pelvic extenteration (TPE) and the tumor depth was more than 5 mm of invasion in the paracolpium, salvage HDR-ISBT was applied. RESULTS: A total of 26 patients were included in this study. The median number of fractions and dose per fraction of HDR-ISBT were 5 (range=3-20 fractions) and 6 Gy (range=2.5-6 Gy), respectively. Three-year local control, progression-free survival, and overall survival were 51.1%, 34.4% and 57.1%, respectively. Combination of external-beam radiation therapy, clinical target volume D90 greater than 65 Gy, and dose per fraction greater than 5 Gy were associated with favorable local control. CONCLUSION: For patients with recurrent cervical cancer post hysterectomy who are not candidates for TPE, salvage HDR-ISBT is a possible curative treatment modality.

[This corrects the article DOI: 10.5114/jcb.2015.54968.].

BACKGROUND: The radiation field for patients with postoperative head and neck squamous cell carcinoma is narrower in our institution than in Western countries to reduce late radiation related toxicities. This strategy is at a risk of loco-regional or distant metastasis. However, because patients are more closely checked than in Western countries by every 1 to 2 months intervals and it is supposed that regional recurrences are identified and salvage surgeries are performed more quickly. Therefore, it is considered that patient survival would not be compromised with this strategy. The aim of this study was to investigate the feasibility of this strategy retrospectively. METHODS: Patients who underwent neck dissection with close or positive margin, extra-capsular spread (ECS), multiple regional lymph node metastasis, pT4, with or without primary tumor resection were treated with postoperative radiation therapy. The volume of radiation field, especially the coverage of prophylactic regional lymph node area, was discussed among head and neck surgeons and radiation oncologists taking into account the clinical factors including patient's age, performance status, number of positive lymph nodes, size of metastatic lymph nodes, extension of primary tumor beyond the midline, and existence of ECS. RESULTS: Seventy-two patients were identified who were treated with postoperative radiation therapy for head and neck squamous cell carcinoma between November 2005 and December 2014. There were 20 patients with oropharynx, 19 with hypopharynx, 7 with larynx, 23 with oral cavity, and 3 with other sites. Thirty eight patients had their neck irradiated bilaterally and 34 unilaterally. Median follow-up period for patients without relapse was 20.7 months (5.1-100.7). Thirty two patients had disease relapse after treatment including 22 loco-regional recurrence and 14 distant metastases. Among 22 loco-regional recurrence, seven patients underwent salvage surgery and one of them was no relapse at the time of the analysis. Among patients without bilateral neck lymph node metastasis who were treated with unilateral neck irradiation, patients with oral cavity or recurrent disease had significantly lower DFS compared with those without (2-y DFS 41.7 % vs 88.2 %, p = 0.017). CONCLUSIONS: In patients without bilateral neck lymph node involvement, the postoperative unilateral neck irradiation is a reasonable treatment strategy for patients with the exception of oral cavity or recurrent disease.

Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy).

PURPOSE: The endobronchial brachytherapy (EBBT) is an established treatment method for tumors of the tracheobronchial system, however, little is known about the tolerance dose for organ at risk (OAR) in EBBT. The purpose of this study is to analyze patients with superficial bronchial carcinoma treated with definitive EBBT, and to investigate a relationship between late complications and dose for OAR. MATERIAL AND METHODS: Endobronchial brachytherapy was performed 6 Gy per fraction for three to four fractions with or without external beam radiation therapy (EBRT). For the purpose of dosimetric analysis, the wall of the lower respiratory tract (LRT: trachea, main bronchus, and lobar bronchiole), trachea, and main bronchus (TMB) was extracted. D0.5cc, D1cc, and D2cc of LRT and TMB were calculated in each EBBT session and added together. V100, V150, and V200 of LRT were also calculated. RESULTS: Between March 2008 and April 2014, EBBT was performed in 14 patients for curative intent. The 2-year overall survival (OS), progression-free survival (PFS), and local recurrence free survival (LRFS) was 82.1%, 77.9%, and 91.7%, respectively. There was one patient with grade 5, one grade 4, and three grade 3 obstruction of trachea or bronchus. The mean EQD2 of LRT D2cc, TMB D2cc, D1cc, and D0.5cc of patients with or without late severe respiratory complications was significantly different between two groups (p = 0.018, 0.008, 0.009, and 0.013, respectively). The 2-year incidence rates of late severe complications in patients with TMB D2cc ≤ 85 Gy in EQD2 and > 85 Gy were 0% and 83.3%, respectively with a statistically significance (p = 0.014). CONCLUSIONS: It was discovered that TMB D2cc > 85 Gy in EQD2 is a strong risk factor for severe late respiratory complication after EBBT.

PURPOSE: Concurrent administration of Cetuximab with radiotherapy (Cetuximab-radiation) has been accepted as an alternative option for locally advanced head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to retrospectively compare complications of Cetuximab-radiation with those of concurrent chemoradiation (cCRT) with a special concern on gastrointestinal (GI) hemorrhage associated with Cetuximab-radiation. METHODS: Indication of Cetuximab-radiation/cCRT for locally advanced HNSCC was primary, postoperative adjuvant, or salvage after recurrence. Our first choice for patients with advanced HNSCC was cCRT; however, if patients did not have enough organ function but with a favorable performance status, Cetuximab-radiation was applied. RESULTS: From April 2013 to March 2014, 30 patients were identified who were treated with Cetuximab-radiation or cCRT and each cohort consisted of 15 patients. Patients in Cetuximab-radiation cohort suffered from a statistically higher rate of G3/4 dermatitis compared with cCRT cohort (80 vs. 13.3%, respectively, p < 0.001). More patients required unexpected hospitalization due to deterioration of their general condition and total parenteral nutrition in Cetuximab-radiation cohort (p = 0.011 and p = 0.025, respectively). While none experienced GI bleeding in cCRT cohort, four patients experienced GI bleeding including two grade 4 bleeding in Cetuximab-radiation cohort (p = 0.05). CONCLUSIONS: It is probable that there exists a group of patients who are susceptible for Cetuximab-radiation not only in terms of well-known dermatitis and mucositis but also of gastrointestinal complications.

OBJECTIVES/HYPOTHESIS: Treatment of head and neck squamous cell carcinoma (HNSCC) often requires radiotherapy, but relapse can occur. There is, therefore, an urgent need for the identification of a predictive novel biomarker for radiosensitivity. The epithelial cell adhesion molecule (EpCAM) has been shown to promote the transformation of malignant tumors, and EpCAM may have prognostic significance, but it is not known if EpCAM determines prognosis, especially with respect to radiotherapy. Therefore, we determined the incidence of the expression of EpCAM in HNSCC and analyzed the prognostic value in patients with early-stage glottic cancer treated with radiotherapy. STUDY DESIGN: Retrospective analysis. METHODS: All patients with HNSCCs examined in our hospital between January 2012 and February 2013 were analyzed prospectively for the expression of EpCAM. T1-2N0 glottic cancer patients who were primarily treated by radiation therapy between 1995 and 2008 were retrospectively investigated. Patients with or without local recurrence after radical radiation therapy were extracted. The relationship between local recurrence and histopathologic EpCAM expression was compared within these two groups. RESULTS: One hundred eighteen patients with HNSCCs from the nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, paranasal cavity, unknown primary, and other sites were analyzed. Positive expression of EpCAM was noted in the oropharynx, hypopharynx, and larynx (72%, 90%, and 58%, respectively). Seventeen and 22 patients with or without local recurrence were extracted, respectively. There was no difference between two groups, with the exception of EpCAM expression. CONCLUSIONS: The expression of EpCAM in HNSCC was investigated. Patients with strong EpCAM expression were associated with local recurrence after primary radiation therapy. LEVEL OF EVIDENCE: NA

During radiotherapy for gastric lymphoma, it is difficult to protect the liver and kidneys in cases where there is considerable overlap between these organs and the target volume. This study was conducted to compare the three radiotherapy planning techniques of four-fields 3D conformal radiotherapy (3DCRT), half-field radiotherapy (the half-beam method) and intensity-modulated radiotherapy (IMRT) used to treat primary gastric lymphoma in which the planning target volume (PTV) had a large overlap with the left kidney. A total of 17 patients with gastric diffuse large B-cell lymphoma (DLBCL) were included. In DLBCL, immunochemotherapy (Rituximab + CHOP) was followed by radiotherapy of 40 Gy to the whole stomach and peri-gastric lymph nodes. 3DCRT, the half-field method, and IMRT were compared with respect to the dose-volume histogram (DVH) parameters and generalized equivalent uniform dose (gEUD) to the kidneys, liver and PTV. The mean dose and gEUD for 3DCRT was higher than for IMRT and the half-beam method in the left kidney and both kidneys. The mean dose and gEUD of the left kidney was 2117 cGy and 2224 cGy for 3DCRT, 1520 cGy and 1637 cGy for IMRT, and 1100 cGy and 1357 cGy for the half-beam method, respectively. The mean dose and gEUD of both kidneys was 1335 cGy and 1559 cGy for 3DCRT, 1184 cGy and 1311 cGy for IMRT, and 700 cGy and 937 cGy for the half-beam method, respectively. Dose-volume histograms (DVHs) of the liver revealed a larger volume was irradiated in the dose range <25 Gy with 3DCRT, while the half-beam method irradiated a larger volume of liver with the higher dose range (>25 Gy). IMRT and the half-beam method had the advantages of dose reduction for the kidneys and liver.

BACKGROUND/AIM: The purpose of the present study was to compare intensity-modulated radiation therapy (IMRT) plan with (Bone Marrow Sparing (BMS) - IMRT) or without (normal-IMRT) an intention of avoiding bone marrow in order to minimize treatment-related toxicity. PATIENTS AND METHODS: Computed tomography (CT) images of 10 consecutive postoperative cervical cancer patients were used. All patients were already treated by normal-IMRT. BMS-IMRTs were created for this study and dose-volume histogram parameters were compared. RESULTS: Both planning target volume (PTV) D95% and D97% were statistically lower in BMS-IMRT than normal-IMRT, however, the difference was lower than 3%. There were no statistical differences between BMS-IMRT and normal-IMRT in the mean value of rectum V30Gy, V50Gy; bladder V45Gy, V50Gy; Bowel V35Gy, and V50Gy. Both in whole pelvic bone (WPB) and inner cavity of pelvic bone (ICPB), the mean value of V10Gy, V30Gy, and V40Gy of BMS-IMRT were statistically lower than that of normal-IMRT. CONCLUSION: Both lower and higher dose for WPB as well as ICPB were effectively lowered by BMS-IMRT.

PURPOSE: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). METHODS AND MATERIALS: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. RESULTS: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). CONCLUSIONS: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

BACKGROUND: Purpose of this study was to identify predictors of vaginal ulcer after CT based three-dimensional image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancies. METHODS: Records were reviewed for 44 female (14 with primary disease and 30 with recurrence) with gynecological malignancies treated with HDR-ISBT with or without external beam radiation therapy. The HDR-ISBT applicator insertion was performed with image guidance by trans-rectal ultrasound and CT. RESULTS: The median clinical target volume was 35.5 ml (2.4-142.1 ml) and the median delivered dose in equivalent dose in 2 Gy fractions (EQD2) for target volume D90 was 67.7 Gy (48.8-94.2 Gy, doses of external-beam radiation therapy and brachytherapy were combined). For re-irradiation patients, median EQD2 of D(2cc) for rectum and bladder, D0.5cc, D(1cc), D(2cc), D(4cc), D(6cc) and D(8cc) for vaginal wall was 91.1 Gy, 100.9 Gy, 260.3 Gy, 212.3 Gy, 170.1 Gy, 117.1 Gy, 105.2 Gy, and 94.7 Gy, respectively. For those without prior radiation therapy, median EQD2 of D(2cc) for rectum and bladder, D(0.5cc), D(1cc), D(2cc), D(4cc), D(6cc) and D(8cc) for vaginal wall was 56.3 Gy, 54.3 Gy, 147.4 Gy, 126.2 Gy, 108.0 Gy, 103.5 Gy, 94.7 Gy, and 80.7 Gy, respectively. Among five patients with vaginal ulcer, three had prior pelvic radiation therapy in their initial treatment and three consequently suffered from fistula formation. On univariate analysis, re-irradiation and vaginal wall D(2cc) in EQD2 was the clinical predictors of vaginal ulcer (p = 0.035 and p = 0.025, respectively). The ROC analysis revealed that vaginal wall D(2cc) is the best predictor of vaginal ulcer. The 2-year incidence rates of vaginal ulcer in the patients with vaginal wall D(2cc) in EQD2 equal to or less than 145 Gy and over 145 Gy were 3.7% and 23.5%, respectively, with a statistically significant difference (p = 0.026). CONCLUSIONS: Re-irradiation and vaginal D(2cc) is a significant predictor of vaginal ulcer after HDR-ISBT for gynecologic malignancies. Three-dimensional image-guided treatment planning should be performed to ensure adequate target coverage while minimizing vaginal D(2cc) in order to avoid vagina ulcer.

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V100 achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D100 was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D90 was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D2cm(3): 408 ± 71 cGy vs manual optimization D2cm(3): 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D2cm(3): 452 ± 60 cGy vs manual optimization D2cm(3): 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.

BACKGROUND: There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. METHODS: The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. RESULTS: There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. CONCLUSION: There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma, especially of diffuse large B-cell lymphoma.