Prognostic factors of dose-response relationship for nodal control in metastatic lymph nodes of cervical cancer patients undergoing definitive radiotherapy with concurrent chemotherapy.

OBJECTIVE: Regional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer. METHODS: We identified 115 patients with 417 metastatic nodes who received definitive CRT for cervical cancer with nodal metastases. External beam radiation therapy and brachytherapy plans were summated to determine total dose received by each node. Prognostic factors of nodal control and dose-response relationship were investigated using Cox-regression and restricted cubic spline function. RESULTS: The 2-year progression-free survival rate was 69.4%. Among 43 patients with failures, 17 patients (37.5%) had regional failure included in first failure sites of which all except one were in-field only regional failures. Total 30 nodes showed recurrence at initial metastatic site after treatment. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, total radiation dose (minimum dose received by 98% of the target volume in equivalent dose in 2 Gy per fractions), and initial nodal volume ≥5.29 mL were poor prognostic factors (all p<0.050) of nodal local control. Restricted cubic spline functions revealed strongest dose-response relationship in high NLR (NLR ≥3.1) and initial nodal volume ≥5.29 mL subgroup. CONCLUSION: Initial nodal volume, radiation dose, and NLR were significant factors of nodal local control in cervical cancer; a stronger dose-response relationship was seen in bulky nodes with high NLR. Clinicians may consider these factors when determining the RT dose and the need for boost to nodal metastases in cervical cancer.

Radiotherapy is a safe and effective salvage treatment for recurrent cervical cancer.

OBJECTIVE: The feasibility of salvage radiotherapy (RT) for patients with recurrent cervical cancer after definitive treatment is contentious. The purpose of this study was to investigate the feasibility and benefit of RT, particularly intensity-modulated RT (IMRT), for salvage treatment in patients with recurrent cervical cancer. METHODS: We retrospectively analyzed 125 patients with recurrent cervical cancer treated with RT at Yonsei Cancer Center between January 2007 and December 2016. All patients received salvage RT for the recurred or metastatic tumor mass. Irradiating dose and volume were determined depending on initial treatment. IMRT was selected in challenging cases, such as re-irradiation or for patients for whom implementing a satisfactory 3-dimensional conformal RT plan was challenging. RESULTS: The median follow-up period was 5.5 years (range, 10.8 months to 41 years). The 5-year local failure-free survival (LFFS) and progression-free survival (PFS) rates were 63.9% and 39.6%, respectively. The 5-year overall survival (OS) rate was 66%; 10-year OS reached 51%. The median PFS rates in patients with locoregional failure, distant metastases, or both were 45.4, 29.1, and 14.7 months, respectively (p = 0.005). For the 45 patients that received re-irradiation, 5-year LFFS, PFS, and OS rates were 47.1%, 33.2%, and 66.5%, respectively. Late complications were observed in 12 patients (12/125, 9.6%). CONCLUSIONS: Our data suggest that salvage RT is safe and effective against recurrent cervical cancer. IMRT is a safe and effective salvage modality for these patients, including those requiring re-irradiation.

Radiation recall dermatitis triggered by sorafenib after radiation therapy for hepatocellular carcinoma.

Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment. Eleven days after starting sorafenib, the patient complained of erythematous rash with pruritus in the chest wall, in a location consistent with the previous radiation field. Sorafenib was continued at the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks without any medical intervention.

The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea.

PURPOSE: To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. MATERIALS AND METHODS: Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). RESULTS: The age range was 26-87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. CONCLUSION: Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients.

Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer.

OBJECTIVE: We aimed to assess the efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S), and compared the clinical outcome with that of concurrent chemoradiotherapy (CCRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) IB-IIB cervical cancer. METHODS: We reviewed 85 patients with FIGO IB-IIB cervical cancer who received NACT+S between 1989 and 2012, and compared them to 358 control patients who received CCRT. The clinical application of NACT was classified based on the following possible therapeutic benefits: increasing resectability after NACT by reducing tumor size or negative conversion of node metastasis; downstaging adenocarcinoma regarded as relatively radioresistant; and preservation of fertility through limited surgery after NACT. RESULTS: Of 85 patients in the NACT+S group, the pathologic downstaging and complete response rates were 68.2% and 22.6%, respectively. Only two young patients underwent limited surgery for preservation of fertility. Patients of the NACT+S group were younger, less likely to have node metastasis, and demonstrated a higher proportion of FIGO IB cases than those of the CCRT group (p≤0.001). The 5-year locoregional control, progression-free survival, and overall survival rates in the NACT+S group were 89.7%, 75.6%, and 92.1%, respectively, which were not significantly different from the rates of 92.5%, 74%, and 84.9% observed in the CCRT group, respectively (p>0.05). CONCLUSION: NACT+S has no therapeutic advantages over CCRT, the standard treatment. Therefore, NACT+S should be considered only in selected patients through multidisciplinary discussion or clinical trial setting.

Volumetric modulated arc therapy for carotid sparing in the management of early glottic cancer.

PURPOSE: Radiotherapy of the neck is known to cause carotid artery stenosis. We compared the carotid artery dose received between volumetric modulated arc therapy (VMAT) and conventional fixed-field intensity-modulated radiotherapy (IMRT) plans in patients with early glottic cancer. MATERIALS AND METHODS: Twenty-one early glottic cancer patients who previously underwent definitive radiotherapy were selected for this study. For each patient, double arc VMAT, 8-field IMRT, 3-dimensional conformal radiotherapy (3DCRT), and lateral parallel-opposed photon field radiotherapy (LPRT) plans were created. The 3DCRT plan was generated using lateral parallel-opposed photon fields plus an anterior photon field. VMAT and IMRT treatment plan optimization was performed under standardized conditions to obtain adequate target volume coverage and spare the carotid artery. Dose-volume specifications for the VMAT, IMRT, 3DCRT, and LPRT plans were calculated with radiotherapy planning system. Monitor units (MUs) and delivery time were measured to evaluate treatment efficiency. RESULTS: Target volume coverage and homogeneity results were comparable between VMAT and IMRT; however, VMAT was superior to IMRT for carotid artery dose sparing. The mean dose to the carotid arteries in double arc VMAT was reduced by 6.8% compared to fixed-field IMRT (p < 0.001). The MUs for VMAT and IMRT were not significantly different (p = 0.089). VMAT allowed an approximately two-fold reduction in treatment delivery time in comparison to IMRT (3 to 5 minutes vs. 5 to 10 minutes). CONCLUSION: VMAT resulted in a lower carotid artery dose compared to conventional fixed-field IMRT, and maintained good target coverage in patients with early glottic cancer.

Oncocytic Schneiderian Papilloma of the Sinonasal Tract Treated With Radiotherapy.

A 66-year-old man visited the ophthalmology department due to epiphora and was subsequently diagnosed with oncocytic schneiderian papilloma. Surgical removal was recommended to the patient; however, he refused this option. Therefore, a radiation of 64 gray (Gy) was administered in 32 daily doses (2 Gy daily) over 45 days using intensity-modulated radiotherapy. Four months after radiotherapy, the tumor had disappeared. Two years postradiotherapy, the patient was healthy, without tumor recurrence or the development of orbital complications. The authors suggest that radiotherapy could be an adjuvant or definite treatment modality for patients of oncocytic schneiderian papilloma unsuitable for complete surgical removal, or those associated with a high risk of surgery-related complications.

Definitive Chemoradiotherapy Versus Surgery Followed by Adjuvant Radiotherapy in Resectable Stage III/IV Hypopharyngeal Cancer.

PURPOSE: The purpose of this study is to compare the treatment outcomes for locally advanced resectable hypopharyngeal cancer between organ-preserving chemoradiotherapy (CRT) and surgery followed by radiotherapy (SRT). MATERIALS AND METHODS: We reviewed 91 patients with stage III/IV hypopharyngeal squamous cell carcinoma treated with radiotherapy (RT). In the CRT group (n=34), 18 patients were treated with concurrent CRT and 16 patients with induction chemotherapy plus concurrent CRT. In the SRT group (n=57), six patients were treated with total laryngopharyngectomy, 34 patients with total laryngectomy (TL) and partial pharyngectomy (PP), and 17 patients with PP, which were followed by adjuvant radiotherapy (n=41) or CRT (n=16). The median RT dose was 70 Gy for CRT and 59.4 Gy for SRT. RESULTS: Five-year local control (84.1% vs. 90.9%), and disease-free survival (DFS, 51.0% vs. 52.7%) and overall survival (OS, 58.6% vs. 56.6%) showed no significant difference between the CRT and SRT groups. The functional larynx-preservation rate was higher in the CRT group (88.2% vs. 29.8%). Treatment-related toxicity, requiring surgical intervention, occurred more frequently in the SRT group (37% vs. 12%). In the SRT group, TL resulted in a significantly higher DFS than larynx-sparing surgery (63.9% vs. 26.5%, p=0.027). Treatment outcome of the SRT group improved when only patients with TL were considered (n=40); however, 5-year OS (67.1% vs. 58.6%, p=0.830) and DFS (63.9% vs. 51.0%, p=0.490) did not improve significantly when compared to the CRT group. CONCLUSION: Organ preserving CRT provided a treatment outcome that is comparable to SRT for locally advanced hypopharyngeal cancer, while offering an opportunity for functional larynx-preservation and reduced treatment-related toxicity.

Optimal Extent of Prophylactic Irradiation of Paraaortic Lymph Nodes in Patients with Uterine Cervical Cancer.

PURPOSE: The purpose of this study was to determine optimal extent of prophylactic irradiation of paraaortic lymph nodes (PALN) in patients with uterine cervical cancer who had metastatic pelvic LNs. METHODS AND MATERIALS: We retrospectively evaluated 103 patients with cervical cancer and pelvic lymph node metastasis who were treated with prophylactic semi-extended field radiotherapy (SEFRT) between 1990 and 2012. The semi-extended field included PALN below the second lumbar spine with prescribed doses of 45 to 50 Gy. Survival outcomes were calculated using the Kaplan-Meier method, and acute and late toxicities were scored using the Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer toxicity criteria. RESULTS: The median follow-up after SEFRT was 61 (range 5-296) months. Overall, 28 patients (27.2%) experienced treatment failures, which were classified as local in 8 patients (7.8%), regional in 8 patients (7.8%), and distant in 13 patients (12.6%). Of the regional failures, only two involved PALN failure around the renal artery or the renal hilum area at the upper margin of the semi-extended field. At 5 years, the overall survival was 82%. Grade 3 or higher acute gastrointestinal and genitourinary toxicities occurred in one and two patients, respectively. As a late toxicity, one patient developed grade 3 small bowel obstruction. CONCLUSION: Prophylactic SEFRT provided favorable outcomes with little acute or late gastrointestinal toxicity. For prophylaxis of PALN recurrences, upper part of PALN might not need to be included in patients with uterine cervical cancer and metastatic pelvic LNs.

De-escalation of the cumulative central radiation dose according to the tumor response can reduce rectal toxicity without compromising the treatment outcome in patients with uterine cervical cancer.

OBJECTIVE: To assess the treatment outcome and toxicity of a low cumulative central dose using a midline block (MLB) during external beam radiotherapy (EBRT). METHODS: Between January 1988 and December 2010, 1559 patients with FIGO stage IB-IIB uterine cervical cancer that underwent EBRT and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were retrospectively analyzed. During EBRT, MLB was performed (n=1195, MLB group) when a sufficient response was achieved to insert the tandem through the cervical canal and place ovoids in the vaginal cavity. MLB was not applied for patients with a slow tumor response (n=364, non-MLB group). The doses were estimated according to the International Commission on Radiation Units and Measurements (ICRU) points. The biologically equivalent dose in 2-Gy fractions (EQD2) was calculated to estimate the cumulative dose from EBRT and ICBT. RESULTS: EQD2pointA, EQD2rectum, and EQD2bladder were all significantly lower in the MLB group (all P<0.05). The 10-year grade≥2 late rectal toxicity rate was significantly lower in the MLB group (P=0.012), while there was no significant difference in late genitourinary and small bowel toxicity. ICRU rectal and bladder doses showed significant predictability on late rectal and bladder toxicities. After propensity score matching, all patient and tumor characteristics were well matched and the survival and recurrence rates between the two groups were similar (all P>0.05), despite the lower EQD2pointA in the MLB group (P<0.001). CONCLUSIONS: Applying MLB according to tumor response during EBRT lowered the cumulative central dose and reduced late rectal toxicity without compromising treatment outcome.

Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer.

PURPOSE: To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. RESULTS: The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. CONCLUSION: Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in these patients.

Tailored radiotherapeutic strategies for disseminated uterine cervical cancer patients.

BACKGROUND: To investigate the role of radiotherapy (RT) in and to suggest radiotherapeutic strategies for patients presenting with disseminated cervical cancer. METHODS: We retrospectively analyzed 50 patients diagnosed as the disseminated cervical cancer with distant lymph nodal or visceral organ metastasis between September 1980 and August 2012. Patients were divided into two subgroups according to visceral organ metastasis: 35 patients diagnosed with distant lymph node metastasis only (group A) and 15 patients with visceral organ metastasis (group B). All patients received external beam RT to the pelvis (median dose 45 Gy) and high-dose rate intracavitary RT (median dose 30 Gy). Thirty-nine patients (78%) received chemotherapy. RESULTS: Median follow-up time was 74 months. The 5-year pelvic control rate (PCR) was 85.8%, and the progression-free survival (PFS), and overall survival (OS) rates were 28.7%, and 36.2%, respectively. The major treatment failure was systemic progression (32 patients, 64%). The 5-year PCRs in groups A and B were 87.4% and 74.7%, respectively (p > 0.05). Meanwhile, PFS and OS rates for group A were significantly better than those for group B (35.3% vs. 13.3%, p = 0.010; and 46.3% vs. 13.3%, p = 0.009, respectively). CONCLUSION: Our data revealed considerable prognostic heterogeneity in disseminated cervical cancer. Even though a high PCR was achieved in patients treated with definitive RT, survival outcomes were dependent on progression of visceral organ metastasis. Therefore, personalized RT and chemotherapy treatment strategies according to the presence of visceral organ metastasis in disseminated cervical cancer patients may help improve clinical outcomes.

Treatment outcomes of extended-field radiation therapy and the effect of concurrent chemotherapy on uterine cervical cancer with para-aortic lymph node metastasis.

PURPOSE: To review the clinical outcomes of extended-field radiation therapy (EFRT) and to analyze prognostic factors significant for survival in patients receiving EFRT for uterine cervical carcinoma with para-aortic node (PAN) metastasis. PATIENTS AND METHODS: We retrospectively reviewed 90 patients with stage IB-IVA cervical cancer and PAN metastasis between 1987 and 2012. Median age was 50 (range, 24-77). Patients received median 70.2 Gy (range, 56-93) to point A and median 50.4 Gy (range, 45-60.4) to PAN over median 69 elapsed days (range, 43-182). Forty-six patients (51.1%) received concurrent chemotherapy. Survival was calculated using the Kaplan-Meier method. We analyzed prognostic factors for overall actuarial survival (OS) and progression-free survival (PFS) using a Cox regression method. RESULTS: The median follow-up period for surviving patients was 55 months (range, 3-252). Seventy patients (77.8%) had complete remission. Forty-six patients experienced treatment failure as follows: 11 patients (12.2%) as local recurrence, 19 (21%) as regional recurrence and 33 (36.7%) as distant metastasis. The 5-yr OS and PFS were 62.6% and 43.9%, respectively. Treatment response was the only statistically independent prognostic factors for OS (p= 0.04) and PFS (p< 0.001) on multivariate analysis. Grade 3 or 4 hematologic gastrointestinal and urogenital toxicities were observed in about 10% of patients. CONCLUSIONS: Our institutional experiences showed that EFRT was an effective treatment for cervical cancer patients with PAN metastasis. The addition of chemotherapy to EFRT seems to have uncertain survival benefit with higher hematologic toxicity.

Radiation recall dermatitis induced by tamoxifen during adjuvant breast cancer treatment.

Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week.

Risk stratification of abdominopelvic failure for FIGO stage III epithelial ovarian cancer patients: implications for adjuvant radiotherapy.

OBJECTIVE: To analyze patterns of abdominopelvic failures and to define subgroups for the use of adjuvant radiotherapy in the International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer (EOC). METHODS: We reviewed 149 patients treated with debulking surgery followed by intravenous taxane and platinum chemotherapy between 1999 and 2008. Patient characteristics, patterns of failure, abdominopelvic failure APF-free survival (APFFS) and overall survival (OS) were analyzed. RESULTS: The median age of the patients was 51 years. Thirty-two patients (21.5%) were found to have residuum >2 cm after surgery. The median pretreatment CA-125 was 604 and 54.4% of patients had a decline in CA-125 ≥90% between pretreatment and at postoperative 1 month. With a median follow-up of 50 months, 79 patients (53.0%) experienced abdominopelvic failure (APF). The 5-year APF-free survival rate was 41.1%. Lymph node metastasis, size of residual disease, and decline in CA-125 were found to be significant prognostic factors for APF upon multivariate analysis. The group of patients in whom abdominopelvic irradiation was indicated as definitive postoperative treatment comprised 55% of the overall patient population and their 5-year survival rate was 68%. CONCLUSION: The stratification was suggested to predict APF based on lymph node metastasis, size of residual tumor, and decline in CA-125. Adjuvant radiotherapy covering the whole abdominopelvis using the intensity modulation technique may be considered to reduce APF in FIGO stage III EOC patients with intermediate risk.

Mechanism of enhancement of radiation-induced cytotoxicity by sorafenib in colorectal cancer.

Sorafenib, an orally available multikinase inhibitor, combined with radiation has shown potential as an anticancer treatment in an in vitro and in vivo colon cancer model. In this study, we investigated the mechanism of enhancement of radiation-induced cytotoxicity by sorafenib in colorectal cancer. The effects of sorafenib on radiation-induced cytotoxicity of DLD-1 and HT-29 were evaluated via clonogenic assay. The impact of sorafenib on radiation-induced cell cycle kinetics and on apoptosis was analyzed using flow cytometry. Cyclin B1 was examined by western blot. As a measure of DNA damage after treatment, γ-H2AX foci and nuclear fragmentation were determined as a function of time after irradiation plus sorafenib combination. Tumor growth delay was used to evaluate the effects of sorafenib on in vivo radiation-induced cytotoxicity. Exposure of each cell line to sorafenib combined with irradiation resulted in an increased radiation-induced cytotoxicity with dose enhancement factors at a surviving fraction of 0.37 ranging from 1.13 to 1.76. Sorafenib strengthened radiation-induced accumulation of tumor cells in the G2-M phase with attenuated expression of cyclin B1, but had no effect on radiation-induced apoptosis. Exposure to sorafenib and radiation resulted in a greater number of remaining γ-H2AX foci and fragmented nuclei than radiation alone. In vivo tumor xenograft study confirmed that administration of sorafenib results in significant tumor growth inhibition when combined with radiation. These results indicate that sorafenib enhances radiation-induced cytotoxicity in colorectal cancer and suggest that the mechanism is associated with delaying repair of radiation-induced DNA damage and down-regulation of cyclin B1.

IMRT with simultaneous integrated boost and concurrent chemotherapy for nasopharyngeal cancer: plan evaluation and treatment outcome.

OBJECTIVE: This study evaluated the outcome of intensity-modulated radiation therapy with simultaneous integrated boost and concurrent chemotherapy for nasopharyngeal cancer. METHODS: We analyzed 53 consecutive nasopharyngeal cancer patients who received definitive treatment using intensity-modulated radiation therapy with simultaneous integrated boost and cisplatin-based concurrent chemotherapy. Forty-six patients were treated with concurrent chemoradiation and seven patients with induction chemotherapy plus concurrent chemoradiation. The gross tumor (PTV(70)) received 69.96 Gy (2.12 Gy/fraction), high-risk subclinical disease (PTV(60)) received 59.4 Gy (1.8 Gy/fraction) and low-risk subclinical disease (PTV(56)) received 56.1 Gy (1.7 Gy/fraction) in 33 fractions. Twenty-eight patients were treated with step-and-shoot intensity-modulated radiation therapy and 25 patients with helical tomotherapy. Dosimetric parameters were compared between the two modalities. RESULTS: The median treatment duration was 49 days (range: 41-65 days). The complete response rate was 92.5%. Three local, two regional, one locoregional and seven distant failures were observed. With the median follow-up of 41 months (range: 8-89 months), the 3- and 5-year local control, locoregional control, disease-free survival and overall survival rates were 91.8 and 91.8%; 87.6 and 87.6%; 77.5 and 70.5%; and 86.4 and 82.1%, respectively. Grade 3 mucositis, dermatitis, leucopenia and grade 4 leucopenia were observed in 10, 1, 2 and 1 patient, respectively. No grade 3 or higher xerostomia occurred. Helical tomotherapy significantly improved dosimetric parameters including the maximum dose, volume receiving >107% of the prescribed dose and uniformity index (D(5)/D(95)). CONCLUSIONS: Intensity-modulated radiation therapy with simultaneous integrated boost with concurrent chemotherapy is a safe and effective treatment modality for nasopharyngeal cancer. Helical tomotherapy has a dosimetric advantage over step-and-shoot intensity-modulated radiation therapy in a clinical setting.

High-dose-rate intracavitary radiotherapy in the management of cervical intraepithelial neoplasia 3 and carcinoma in situ presenting with poor histologic factors after undergoing excisional procedures.

PURPOSE: To assess the effectiveness of high-dose-rate intracavitary radiotherapy (HDR-ICR) in patients with cervical intraepithelial neoplasia 3 (CIN 3) and carcinoma in situ (CIS) presenting with poor histologic factors for predicting residual disease after undergoing diagnostic excisional procedures. METHODS AND MATERIALS: This study was a retrospective analysis of 166 patients with CIN 3 (n=15) and CIS (n=151) between October 1986 and December 2005. They were diagnosed by conization (n=158) and punch biopsy (n=8). Pathologic analysis showed 135 cases of endocervical gland involvement (81.4%), 74 cases of positive resection margins (44.5%), and 52 cases of malignant cells on endocervical curettage (31.3%). All patients were treated with HDR-ICR using Co6° or Ir¹9² at a cancer center. The dose was prescribed at point A located 2 cm superior to the external os and 2 cm lateral to the axis of the tandem for intact uterus. RESULTS: Median age was 61 years (range, 29-77). The median total dose of HDR-ICR was 30 Gy/6 fractions (range, 30-52). At follow-up (median, 152 months), 2 patients developed recurrent diseases: 1 CIN 2 and 1 invasive carcinoma. One hundred and forty patients survived and 26 patients died, owing to nonmalignant intercurrent disease. Rectal bleeding occurred in one patient; however, this symptom subsided with conservative management. CONCLUSIONS: Our data showed HDR-ICR is an effective modality for CIN 3 and CIS patients presenting with poor histologic factors after excisional procedures. HDR-ICR should be considered as a definitive treatment in CIN 3 and CIS patients with possible residual disease after undergoing excisional procedures.

Is there a clinical benefit to adaptive planning during tomotherapy in patients with head and neck cancer at risk for xerostomia?

OBJECTIVES: To evaluate the necessity of adaptive planning in helical tomotherapy (TOMO) for head and neck cancer in terms of dosimetric influence on the parotid gland. METHODS: Thirty-one patients underwent curative TOMO for head and neck cancer from April 2006 to April 2007. For each patient, neck diameter was monitored together with body weight at first cervical spine level through mega-voltage computed tomography during the TOMO course. Ten of 31 patients, with significant weight loss (>5%) and/or neck diameter decrease (>10%), were selected for dosimetric analysis, and parotid dose was recalculated at the fourth and last week of TOMO. Xerostomia was estimated by Radiation Therapy Oncology Group criteria. RESULTS: The median dose was 69.96 Gy (range, 54 to 69.96 Gy) and there was no grade 3 or greater complication. Ten patients with significant neck diameter decrease and/or weight loss showed frequent grade 2 acute xerostomia (P=0.02). The volume percentage of daily fractional dose over 0.75 Gy for the parotid gland (V0.75 Gy) increased by 23.6% at the end of TOMO. CONCLUSIONS: For patients with significant anatomic contour change; neck diameter decrease (>10%) or weight loss (>5%), adaptive planning using mega-voltage computed tomography can identify dosimetric changes and reduce deleterious side effects such as xerostomia.

Comparison of the efficacy and toxicity between radiotherapy and chemotherapy in nodal and isolated nonnodal recurrence of ovarian cancer.

OBJECTIVES: To assess and compare the efficacy and toxicity of radiotherapy (RT) versus chemotherapy (CT) in patients with nodal and isolated nonnodal recurrence of ovarian cancer. METHODS: Records of 67 patients treated for nodal or isolated nonnodal ovarian cancer recurrence (50 treated with RT and 17 treated with CT) between 2001 and 2010 were retrospectively reviewed. Patients' responses to RT and CT were assessed by the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Progression-free survival and overall survival were calculated using the Kaplan-Meier method. RESULTS: The overall response rate was 64.0% in the RT group and 16.7% in the CT group (P = 0.003). The median follow-up time was 38 months (range, 3-97 months) for RT and 18 months (range, 70-64 months) for CT. The median progression-free survival was 6 months for radiotherapy and 5 months for chemotherapy (P = 0.212). Median overall survival between the 2 groups was not significantly different (P = 0.246). There was no RT-mediated grade 3 or 4 hematologic toxicity, but overall toxicity was not significantly different between the 2 groups. CONCLUSIONS: Radiotherapy resulted in a better response and tolerable toxicities compared to CT in patients with either nodal or isolated nonnodal ovarian cancer recurrence. However, progression-free survival and overall survival did not differ between RT and CT. A prospective, multicenter, randomized controlled study is needed to evaluate the survival benefits of RT for ovarian cancer.