Malignant myoepithelioma in the maxillary sinus: case report and review of the literature.

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy.

Proton beam therapy for hepatocellular carcinoma adjacent to the porta hepatis.

PURPOSE: To evaluate the efficacy and safety of proton beam therapy (PBT) for patients with hepatocellular carcinoma (HCC) located adjacent to the porta hepatis. METHODS AND MATERIALS: Subjects of the study were 53 patients with HCC located within 2 cm of the main portal vein. All patients had tumor confined to the radiation field with no evidence of metastatic disease. All patients had hepatic function levels of a Child-Pugh score of 10 or less, Eastern Cooperative Oncology Group performance status of 2 or less, and no uncontrolled ascites. Patients underwent PBT of 72.6 GyE in 22 fractions from Sept 2001 to Dec 2004. RESULTS: After 3 years, the actuarial survival rate was 45.1% and local control rate was 86.0%. Prognostic factors for survival included Child-Pugh score, number of tumors, and alpha-fetoprotein levels. No late treatment-related toxicity of Grade 2 or higher was observed. CONCLUSIONS: The PBT delivering 72.6 GyE in 22 fractions appears to be effective and safe for HCC adjacent to the porta hepatis.

Comparison of tumor regression rate of uterine cervical squamous cell carcinoma during external beam and intracavitary radiotherapy.

PURPOSE: We compared the radioresponse of cervical carcinoma that was closely related to local disease control by the tumor regression rate (RR) during intracavitary radiotherapy (ICRT) and external beam radiotherapy (EBRT) on the presumption that ICRT has a stronger treatment impact than EBRT because of its specific dose distribution. MATERIALS AND METHODS: A total of 37 patients were treated by EBRT at 45.0 Gy over 5 weeks, followed by high-dose-rate ICRT at 6.0 Gy per weekly insertion at point A three to five times and by boost EBRT. RR was defined as the slope (day(-1)) of the tumor-volume shrinkage curve fit to an exponential regression equation. Assuming that the tumors were ellipsoid, the tumor volume was estimated using magnetic resonance (MR) images obtained before treatment, after 45.0 Gy of EBRT, and after the third ICRT insertion. RRs were compared based on the radiotherapy method. RESULTS: RR ranged between -0.008 to 0.093 day(-1) (median 0.021 day(-1)) during EBRT and -0.001 to 0.097 day(-1) (median 0.018 day(-1)) during ICRT, showing no significant difference or correlation between treatments. CONCLUSION: Contrary to expectations, RR did not directly relate to the impact of physical treatment. RR could be related to biological factors, such as the amount of tumor clearance and changes in tumor consistency during treatment.

Hypofractionated high-dose proton beam therapy for stage I non-small-cell lung cancer: preliminary results of a phase I/II clinical study.

PURPOSE: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. RESULTS: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade > or =3 was observed. CONCLUSIONS: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

Proton beam therapy for hepatocellular carcinoma with inferior vena cava tumor thrombus: report of three cases.

Three patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) were treated using proton beam therapy at the University of Tsukuba, Japan. A total dose of 50-70 Gy in 10-35 fractions was given to the primary tumor and IVCTT. All the patients survived for more than 1 year from the beginning of proton beam therapy (13-55 months) and no treatment-related toxicity of grade 3 or higher was observed. These cases suggest that proton beam therapy is safe and effective for patients with HCC associated with IVCTT.

Classical tandem-source dwelling covering the entire uterus: essential in modern intracavitary radiotherapy for cervical cancer?

PURPOSE: We investigated whether conventional tandem-source dwelling to cover the entire uterus, classically regarded as the target volume, is necessary in modern intracavitary radiotherapy (ICRT) for cervical cancer. MATERIALS AND METHODS: The study included 95 cervical squamous cell carcinoma patients treated by high-dose-rate ICRT (point A dose was 6.0 Gy, with three to five insertions per patient) after external beam radiotherapy (EBRT), with central pelvic doses of 12-50 Gy. The tandem-source dwell length was adjusted to the target volume specified by magnetic resonance (MR) imaging. A tandem applicator was inserted as far as the uterine fundus in accordance with the post-EBRT MR-assessed cavity length. The pre-EBRT MR-specified target volume was used for the dwell-length adjustment. The safety of the dwell-length adjustment was assessed in terms of treatment failure. RESULTS: The dwell-length adjustment was made in 248 of 366 total insertions with a dwell-length reduction of 5-55 mm (median 15 mm) at the corpus. Pelvic failure was identified in 22 patients with a 2-year pelvic disease-free survival rate of 75.6% but without evidence of failure at dwelling-skipped corpuses. CONCLUSION: Given after pelvic EBRT and ICRT of full-length dwelling in part, which may have eradicated possible subclinical extension, adjustment of the tandem-source dwell length to the MR-specified target volume appeared to be safe.

Explanation for the failure of neoadjuvant chemotherapy to improve outcomes after radiotherapy for locally advanced uterine cervical cancer from the standpoint of the tumor regression rate.

PURPOSE: Treatment outcomes for patients with locally advanced cervical cancer are no better with neoadjuvant chemotherapy (NAC) combined with radiotherapy (RT) than with RT alone. We investigated the reason for this failure from the standpoint of the tumor regression rate (RR). MATERIALS AND METHODS: A total of 48 patients with clinical stage IIB-IVA cervical squamous cell carcinoma were treated clinically with cisplatin-based NAC plus RT (n = 15) or RT alone (n = 33). The RR was defined as the slope of a tumor shrinkage curve derived with magnetic resonance images. The local control rate (LCR) and disease-free rate (DFR) were estimated by clinical stage (IIB vs. III-IVA), pretreatment volume (< or = median vs. > median), lymph node status (negative vs. positive), treatment type, overall treatment time (< or =8 weeks vs. >8 weeks), and RR (< or = median vs. > median) using univariate and multivariate analyses. RESULTS: RR during NAC or during NAC and RT (n = 15) was not significantly higher than RR by RT alone (n = 33). Low RR and positive nodal status were significantly powerful prognostic factors for both the LCR and DFR, whereas the others were not. CONCLUSION: Although effective in reducing tumor volume prior to RT, NAC showed no overall effect in increasing the RR, which was shown to be the most powerful prognostic factor.

Repeated proton beam therapy for hepatocellular carcinoma.

PURPOSE: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at the University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. RESULTS: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. CONCLUSIONS: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A.

Proton beam therapy for invasive bladder cancer: a prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy.

PURPOSE: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. METHODS AND MATERIALS: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. RESULTS: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently, proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. CONCLUSIONS: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.

Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors.

PURPOSE: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. METHODS AND MATERIALS: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day(-1)) of the shrinkage curve by fitting to an exponential equation. RESULTS: Early-assessed radioresponse ranged from 0.001 to 0.106 day(-1) (median, 0.021 day(-1)) and late-assessed radioresponse from 0.009 to 0.091 day(-1) (median, 0.021 day(-1)), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R(2) = 0.714, p = 0.0005). CONCLUSIONS: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness.

Clinical results of proton beam therapy for cancer of the esophagus.

PURPOSE: To present the results of proton beam therapy for patients with esophageal cancer. METHODS AND MATERIALS: This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1-87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75-89.5 Gy). RESULTS: The 5-year actuarial survival rate for the 46 patients, patients with T1 (n = 23), and those with T2-T4 (n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2-T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2-T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. CONCLUSION: The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.

Preliminary estimation of treatment effect on uterine cervical squamous cell carcinoma in terms of tumor regression rate: comparison between chemoradiotherapy and radiotherapy alone.

PURPOSE: We preliminarily estimated the treatment effect on cervical cancer in terms of the tumor regression rate (TRR) achieved with chemoradiotherapy and radiotherapy alone. MATERIALS AND METHODS: The study included cervical squamous cell carcinomas treated by radiotherapy alone (n=45) or chemoradiotherapy (concurrent once-a-week cisplatin 30 mg/m2, n=13). Tumors were measured three-dimensionally on pre- and mid-treatment magnetic resonance images. TRR was defined as the slope of the exponential regression curve of tumor volume (day(-1)) on the assumption that tumors regressed exponentially with time. RESULTS: TRR ranged widely (0.004-0.090 day-(-1)) and did not significantly differ between treatment with chemoradiotherapy (median, 0.032 day(-1)) and with radiotherapy alone (median, 0.024 day(-1)) (p = 0.361). TRR > 0.05 day(-1) was seen in four chemoradiotherapy tumors (30.8%) and in six radiotherapy-alone tumors (15.0%) (p = 0.207), whereas TRR < 0.01 day(-1) was seen in no chemoradiotherapy tumors (0.0%) and in five radiotherapy-alone tumors (11.1%) (p = 0.180). TRR for tumors > 5.0 cm in diameter was greater with chemoradiotherapy (n=5) than with radiotherapy alone (n=12) (p = 0.065). CONCLUSION: Although the difference did not reach a statistically significant level, our TRR data suggest that concurrent chemotherapy heightens the radioresponse of large-size cervical cancer.

Long-term results of proton beam therapy for carcinoma of the uterine cervix.

PURPOSE: To determine the role of proton therapy in patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Between 1983 and 1991, 25 patients with squamous cell carcinoma of the uterine cervix (stages IIB-IVA) were treated with a curative intent by external photon irradiation to the pelvis, followed by proton irradiation to the primary tumor, delivering a median total tumor dose of 86 Gy (range 71 Gy/26 Fr-101 Gy/46 Fr), and were followed for a median period of 139 months (range 11-184 months). RESULTS: Ten-year overall survival rates for stages IIB and IIIB/IVA patients were 89% and 40%, respectively. Five-year local control rates for stages IIB and IIIB/IVA patients were 100% and 61%, respectively. Four percent of patients experienced severe (Grade 4 or more) late complications in the intestine or urinary bladder at 5 years. CONCLUSION: External photon and proton therapy is effective for those who are not eligible for intracavitary irradiation, and who otherwise have a poor prognosis. The results show that tumor control, survival, and morbidity are similar to those after conventional therapy.

Use of the small pelvic field instead of the classic whole pelvic field in postoperative radiotherapy for cervical cancer: reduction of adverse events.

PURPOSE: We examined whether use of small pelvic (SP) field encompassing only the pericervical regions and upper stream lymphatic will reduce the adverse events that occur with classic whole pelvic (WP) field, in postoperative radiotherapy (RT) for cervical cancer. METHODS AND MATERIAL: This retrospective study included 72 patients treated with SP field (SP group) used specifically for node-negative status and 46 patients treated with WP field (WP group) used conventionally for node-positive status. Total dose was 50.0 or 50.4 Gy at 2.0 or 1.8 Gy per fraction. Acute adverse events (nausea, diarrhea, cystitis, and leukopenia) and late adverse events (lymphedema, cystitis, ileus, and diarrhea) were graded according to the Common Toxicity Criteria and compared between groups. RESULTS: Diarrhea (Grades 2-3) and leukopenia (Grades 1-3) occurred significantly more often in WP group (32.4% and 80.5%, respectively) than in SP group (9.2% and 52.2%, respectively). Among the late events, lymphedema occurred most often overall (5-year rate: SP, 47.0%; WP, 49.1%). Only ileus occurred at a significantly higher rate in The WP group than in SP group (5-year rate: 16.2% vs. 3.2%). CONCLUSIONS: Use of the SP field tailored for node-negative status was suggested to reduce adverse events involving the intestine and hemopoietic system.

Nonoperative assessment of nodal status for locally advanced cervical squamous cell carcinoma treated by radiotherapy with regard to patterns of treatment failure.

PURPOSE: Lymph node metastasis is a major prognostic factor in the treatment of cervical cancer, but its nonsurgical assessment is not necessarily accurate, particularly in small nodes. We evaluated whether node-negative status could be accurately assessed using a low cutoff measure. METHODS AND MATERIALS: The subjects were 84 patients with Stage IIB-IVA cervical squamous cell carcinoma treated by definitive radiotherapy. Nodal status was assessed by CT as negative (<5 mm), possibly positive (5-10 mm), or probably positive (>10 mm). Cause-specific survival and the disease-free rate, including the pelvic recurrence-free and distant metastasis-free rates, were estimated. RESULTS: The cause-specific survival, disease-free rate, and pelvic recurrence-free rate at 5 years were significantly higher for the 32 patients with node-negative disease (83.5%, 86.1%, and 86.1%) and the 17 patients with possibly node-positive disease (59.2%, 93.8%, and 93.8%) than for the 35 patients with probably node-positive disease (32.6%, 22.0%, and 46.8%), respectively. No significant difference was found between negative and possibly node-positive status. In contrast, the distant metastasis-free rate differed significantly among node-negative (96.4%), possibly node-positive (59.3%), and probably node-positive (35.1%) status. CONCLUSION: Node-negative status assessed using a strict cutoff measure may be useful as a strong predictor of cervical cancer being confined to the pelvis.

Clinical evaluation of proton radiotherapy for non-small-cell lung cancer.

PURPOSE: To evaluate the clinical results of proton radiotherapy for patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Between 1983 and 2000, 51 NSCLC patients were treated with proton beams at the University of Tsukuba. There were 28 patients in Stage I, 9 in Stage II, 8 in Stage III, 1 in Stage IV, and 5 with recurrent disease. Thirty-three patients had squamous cell carcinoma, 17 had adenocarcinoma, and 1 had large-cell carcinoma. Median fraction and total doses given were 3.0 Gy (range 2.0-6.0 Gy), and 76.0 Gy (range 49.0-93.0 Gy), respectively. RESULTS: The 5-year overall survival rate was 29% for all patients, 70% for 9 Stage IA patients, and 16% for 19 Stage IB patients, respectively (IA vs. IB: p < 0.05). The 5-year in-field local control rate was higher in patients with Stage IA (89%) when compared with those with Stage IB (39%). Forty-seven patients (92%) experienced acute lung toxicity of Grade 1 or less; 3 had Grade 2, 1 had Grade 3, and none experienced Grade 4 or higher. Patients in the present series showed very little late toxicity. CONCLUSIONS: Proton therapy is a very safe and effective treatment for patients with NSCLC, especially for those with early stages. The relative merit of proton therapy in comparison with stereotactic photon radiotherapy or three-dimensional conformal photon radiotherapy remains to be defined through future clinical trials.

Clinical results of proton beam therapy for skull base chordoma.

PURPOSE: To evaluate clinical results of proton beam therapy for patients with skull base chordoma. METHODS AND MATERIALS: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months). RESULTS: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery. CONCLUSION: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy.

Assessment of cervical cancer radioresponse by serum squamous cell carcinoma antigen and magnetic resonance imaging.

OBJECTIVE: To investigate the possibility of objective clinical assessment of the radioresponse of cervical cancer via determination of serum squamous cell carcinoma antigen levels and magnetic resonance imaging (MRI)-based estimation of tumor shrinkage. METHODS: The cases of 60 patients undergoing definitive radiotherapy for cervical squamous cell carcinoma (stage I-II: n = 20; stage III-IV: n = 40) were reviewed. Measurements of serum squamous cell carcinoma antigen levels (n = 60), estimated tumor volume on preradiotherapy MRIs (n = 60), and evaluated tumor shrinkage on postradiotherapy MRIs available (n = 30) were taken. The relation between postradiotherapy squamous cell carcinoma antigen level 2 months after the start of radiotherapy and disease recurrence was investigated. Regression analysis of tumor volume measured on MRIs was used to estimate the extent of tumor shrinkage 2 months after the start of radiotherapy. RESULTS: Preradiotherapy squamous cell carcinoma antigen levels correlated significantly with preradiotherapy tumor volumes. Recurrence was identified in 27 patients as distant (n = 19), distant and local (n = 1), local (n = 5), or regional (n = 2). Of 51 patients with elevated preradiotherapy squamous cell carcinoma antigen levels, 33 achieved normalized levels after radiotherapy. Squamous cell carcinoma antigen normalization was associated with a higher recurrence-free survival rate at 2 years (74.3%) than that associated with nonnormalization of squamous cell carcinoma antigen (5.6%, P <.001). The extent of shrinkage ranged from 61% to 100%, and there was no local recurrence. CONCLUSION: Postradiotherapy squamous cell carcinoma antigen status is a useful indicator of clinical outcome, particularly about tumor recurrence. It is not, however, useful for assessing response to radiotherapy. Magnetic resonance imaging is useful for obtaining an objective assessment of radioresponse.

Retrospective comparison of clinical outcome between radiotherapy alone and surgery plus postoperative radiotherapy in the treatment of stages IB-IIB cervical squamous cell carcinoma.

PURPOSE: To determine retrospectively whether radical surgery plus postoperative radiotherapy (RT) is superior to definitive RT from the standpoint of disease control and adverse events in the treatment of stages IB-IIA and stage IIB cervical squamous cell carcinoma. MATERIALS AND METHODS: The study included 143 patients treated by definitive RT (stages IB-IIA, n = 15; stage IIB, n = 27) or postoperative RT (stages IB-IIA, n = 67; stage IIB, n = 34). Cause-specific survival (CSS) and recurrence-free rate (RFR) were estimated. Late adverse events (proctitis, cystitis, lymphedema, and ileus) were graded, and the incidences were estimated. RESULTS: Overall, 5-year CSS and RFR did not differ significantly between patients treated with definitive RT (80.4% and 69.7%, respectively) and those treated with postoperative RT (80.6% and 79.1%, respectively). Rates according to clinical stage also did not differ significantly between the two types of treatment. Grades 1-3 adverse events occurred. Grades 2-3 lymphedema and Grades 2-3 ileus, but not Grades 2-3 cystitis, occurred significantly often with postoperative RT. CONCLUSION: Despite no difference in survival or patterns of recurrence, adverse events were significantly more frequent with postoperative RT than with definitive RT for both stages IB-IIA and stage IIB disease.

Genetic variants of NPAT-ATM and AURKA are associated with an early adverse reaction in the gastrointestinal tract of patients with cervical cancer treated with pelvic radiation therapy.

PURPOSE: This study sought to associate polymorphisms in genes related to cell cycle regulation or genome maintenance with radiotherapy (RT)-induced an early adverse reaction (EAR) in patients with cervical cancer. METHODS AND MATERIALS: This study enrolled 243 cervical cancer patients who were treated with pelvic RT. An early gastrointestinal reaction was graded using the National Cancer Institute Common Toxicity Criteria, version 2. Clinical factors of the enrolled patients were analyzed, and 208 patients were grouped for genetic analysis according to their EAR (Grade ≤1, n = 150; Grade ≥2, n = 58). Genomic DNA was genotyped, and association with the risk of EAR for 44 functional single-nucleotide polymorphisms (SNPs) of 19 candidate genes was assessed by single-locus, haplotype, and multilocus analyses. RESULTS: Our analysis revealed two haplotypes to be associated with an increased risk of EAR. The first, comprising rs625120C, rs189037T, rs228589A, and rs183460G, is located between the 5' ends of NPAT and ATM (OR = 1.86; 95% CI, 1.21-2.87), whereas the second is located in the AURKA gene and comprises rs2273535A and rs1047972G (OR = 1.75; 95% CI, 1.10-2.78). A third haplotype, rs2273535T and rs1047972A in AURKA, was associated with a reduced EAR risk (OR = 0.42; 95% CI, 0.20-0.89). The risk of EAR was significantly higher among patients with both risk diplotypes than in those possessing the other diplotypes (OR = 3.24; 95% CI, 1.52-6.92). CONCLUSIONS: Individual radiosensitivity of intestine may be determined by haplotypes in the NPAT-ATM and AURKA genes. These variants should be explored in larger association studies in cervical cancer patients.