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Vulvar cancer is a rare carcinoma constituting only 4% of gynecologic malignancies and 0.6% of female cancers. Most chemotherapy regimens have been created from extrapolation from anal and cervical cancer research. Advanced stages have the worst prognosis and oftentimes invasive surgical procedures are needed to cure disease with high recurrence rates.Case.A 50 yo G2P2 presented for a 2 cm mass in her right labia. The patient underwent a partial radical vulvectomy and bilateral superficial and deep inguinal lymph node dissection. Bilateral inguinal lymph nodes were positive for residual disease. The patient underwent whole pelvic radiation with cisplatin as a radiosensitizer. The primary tumor was epidermal growth factor receptor (EGFR) positive and cetuximab, a monoclonal antibody to EGFR, was added. The patient underwent seven cycles of chemotherapy including cisplatin and cetuximab with adjuvant radiation therapy to the pelvis. She currently is without evidence of disease recurrence since completing treatment 4 years ago.Conclusion.One previous case report showed short-term palliative success of five months for recurrent, metastatic vulvar cancer. This case suggests that cetuximab could possibly be used in initial management of patients with advanced stages of vulvar cancer to improve prognosis.

PurposeTo validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer.Methods and materialsThis study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs>0.1ng/mL) groupings, and clinical outcomes.ResultsThe median follow-up for surviving patients was 9.4years. The median post-neoAS, pre-RT PSA level was 0.3ng/mL, with 32% of patients having levels ≤0.1ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and>0.1ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P0.1ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P0.1ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM).The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity was graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method.Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P.01) and lung V5 (volume receiving 5 Gy or more; P.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated.With increasing experience, target volume coverage improved and dose to the contralateral lung decreased. Rates of pulmonary toxicity were relatively low. However, both local and distant control rates remained suboptimal.

Small cell lung cancer (SCLC) constitutes approximately 16% of all primary lung cancers, with more than 35,000 new cases per year. Two-thirds of patients present with extensive stage disease (ES-SCLC) due to a tendency to metastasize early. Outcomes remain poor, with a median survival of approximately 10 months and a two-year overall survival of

Purpose To report on the safe and effective use of a prostate brachytherapy implant for clinically low-risk prostate cancer in a patient with previous ileal pouch–anal anastomosis. Methods and Materials A patient with a previous history of total proctocolectomy with ileal pouch–anal anastomosis was diagnosed with low-risk prostate cancer. He underwent prostate brachytherapy implant and his urinary, bowel, and sexual function were monitored preoperatively and regularly after his implant. Results Approximately 1-year postimplant, the patient’s serum prostate-specific antigen continued to decrease and urinary obstructive symptoms measured via a standardized patient-reported instrument increased transiently but returned to baseline. His sexual function remains slightly diminished. His self-reported bowel function has been essentially unchanged, and he specifically denies increased stool frequency, urgency, incontinence, tenesmus, or hematochezia. Conclusions Prostate brachytherapy appears to be both safe and effective for treating low-risk prostate cancer in patients with a pre-existing ileal pouch–anal anastomosis. Although there is a potential for significant late injury to the neorectum, a previous small series indicated that this had not been seen. Models currently used to predict normal tissue complication probabilities do not seem well applied to this case. The developments of algorithms that more correctly model this condition are encouraged.

The aim of this paper is to report on the challenges associated with identifying disease recurrence following combined modality therapy (CMT) for primary lymphoma of the tibia in which an intramedullary nail has been placed. A patient with primary bone lymphoma (PBL) was treated with CMT (chemotherapy and radiation therapy). After a complete response, he has been followed for eighteen months by physical exam and radiographic imaging. Despite persistent increased tracer accumulation at the original site, he has no proven recurrence. Literature review showed a small number of retrospective, single institution reviews detailing clinical experience and expected outcome in patients treated with PBL limited to one bony site of disease. PBL presents a treatment challenge, particularly when a weight-bearing long bone is diffusely involved and followup is complicated after placement of stabilizing hardware. Close coordination of the oncology team and diagnostic radiology is required to ensure optimal outcome.

Anal canal cancer is rare, accounting for only 1.3% of all gastrointestinal tract malignancies. Prostate cancer incidence is much higher and accounts for 27.6% of all malignancies in men. Treatment guidelines for anal cancer involve radiotherapy to the primary site and draining lymphatics while treatment for prostate cancer can also include pelvic radiotherapy. The literature is silent on the optimum course of action when these two malignancies are found synchronously or metachronously. Herein, we report a case of a patient diagnosed with intermediate risk prostate cancer who, prior to definitive therapy for this first malignancy, was also diagnosed with anal canal cancer. We conclude that a simultaneous approach with radiation therapy and chemotherapy with subsequent boost to the prostate is recommended. Screening for synchronous prostate cancer in male anal canal cancer patients is probably indicated and may preclude suboptimal treatment for a second occult primary.

Purpose To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low–dose rate brachytherapy. Methods and Materials The biologically effective dose (BED), dose in Gray (Gy) to 90% of prostate (D 90 ), and percent volume of the prostate receiving 100% of the prescription dose (V 100 ) were calculated from the postimplant dose–volume histogram for 140 patients undergoing low–dose rate prostate brachytherapy from 1997 to 2003 at Durham Regional Hospital and the Durham VA Medical Center (Durham, NC). Results The median follow-up was 50 months. There was a 7% biochemical failure rate (10 of 140), and 91% of patients (127 of 140) were alive at last clinical follow-up. The median BED was 148 Gy (range, 46–218 Gy). The median D 90 was 139 Gy (range, 45–203 Gy). The median V 100 was 85% (range, 44–100%). The overall 5-year biochemical relapse-free survival (bRFS) rate was 90.1%. On univariate Cox proportional hazards modeling, no pretreatment characteristic (Gleason score sum, age, baseline prostate-specific antigen, or clinical stage) was predictive of bRFS. The BED, D 90 , and V 100 were all highly correlated (Pearson coefficients >92%), and all were strongly correlated with bRFS. Using the Youden method, we identified the following cut points for predicting freedom from biochemical failure: D 90 ≥ 110 Gy, V 100 ≥ 74%, and BED ≥ 115 Gy. None of the covariates significantly predicted overall survival. Conclusions We observed significant correlation between BED, D 90 , and V 100 with bRFS. The BED is at least as predictive of bRFS as D 90 or V 100 . Dosimetric quantifiers that account for heterogeneity in tumor location and dose distribution, tumor repopulation, and survival probability of tumor clonogens should be investigated.

Purpose To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) after extrapleural pneumonectomy for malignant pleural mesothelioma. Methods and Materials Thirteen patients underwent IMRT after extrapleural pneumonectomy between July 2005 and February 2007 at Duke University Medical Center. The clinical target volume was defined as the entire ipsilateral hemithorax, chest wall incisions, including drain sites, and involved nodal stations. The dose prescribed to the planning target volume was 40–55 Gy (median, 45). Toxicity was graded using the modified Common Toxicity Criteria, and the lung dosimetric parameters from the subgroups with and without pneumonitis were compared. Local control and survival were assessed. Results The median follow-up after IMRT was 9.5 months. Of the 13 patients, 3 (23%) developed Grade 2 or greater acute pulmonary toxicity (during or within 30 days of IMRT). The median dosimetric parameters for those with and without symptomatic pneumonitis were a mean lung dose (MLD) of 7.9 vs. 7.5 Gy ( p = 0.40), percentage of lung volume receiving 20 Gy (V 20 ) of 0.2% vs. 2.3% ( p = 0.51), and percentage of lung volume receiving 5 Gy (V 20 ) of 92% vs. 66% ( p = 0.36). One patient died of fatal pulmonary toxicity. This patient received a greater MLD (11.4 vs. 7.6 Gy) and had a greater V 20 (6.9% vs. 1.9%), and V 5 (92% vs. 66%) compared with the median of those without fatal pulmonary toxicity. Local and/or distant failure occurred in 6 patients (46%), and 6 patients (46%) were alive without evidence of recurrence at last follow-up. Conclusions With limited follow-up, 45-Gy IMRT provides reasonable local control for mesothelioma after extrapleural pneumonectomy. However, treatment-related pulmonary toxicity remains a significant concern. Care should be taken to minimize the dose to the remaining lung to achieve an acceptable therapeutic ratio.

To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low-dose-rate brachytherapy.Generalized equivalent uniform dose (EUD), dose in Gy to 90% of the prostate gland (D(90)), and percentage of the prostate receiving 100% of the prescribed dose (V(100)) were calculated from the postimplant dose-volume histogram (DVH) for 140 patients undergoing low-dose-rate prostate brachytherapy (LDRPB) monotherapy from 1997 to 2003 at Duke University and the Durham VA Medical Center. Biochemical recurrence was defined according to the American Society for Therapeutic Radiology and Oncology consensus definition.Median followup after LDRPB was 50 months. There was a 7% biochemical recurrence rate (10/140) at last clinical followup. The median EUD was 167 Gy (range, 41-245). The median D(90) was 139 Gy (range, 45-203). The median V(100) was 88% (range, 44-100). The overall 5-year biochemical recurrence-free survival (bRFS) was 94.2%. The 5-year bRFS was 100% for EUDor =167 Gy and 89.4% for EUD167 Gy (p=0.008); 100% for D(90)or =140 Gy and 90.4% for D(90)140 Gy (p=0.020); 100% for V(100)or =88%; and 90.3% for V(100)88% (p=0.017). There was no statistically significant correlation between any of these factors and overall survival.In our series of 140 patients with low-risk prostate cancer treated with LDRPB alone, we observed a statistically significant correlation between EUD, D(90), and V(100) and bRFS. The generalized EUD, a calculated value that incorporates the entire prostate DVH, appears to be at least as well correlated with bRFS as D(90) or V(100), and may more completely represent the totality of the dose distribution.

Primary lymphoma of the breast is a rare entity in the field of oncological medicine and represents

A case of monophasic intra-articular synovial sarcoma in the right knee of a 39-year-old active duty serviceman treated with a transfemoral amputation is presented. The patient was evaluated for right knee pain and fullness. After further workup, the patient underwent computed tomographyguided biopsy, with the tissue specimen consistent with intra-articular synovial sarcoma. The patient elected for a transfemoral amputation rather than limb or joint-sparing surgery. The gross specimen measured 3.5 × 3.0 × 1.7 cm in the posteromedial knee. No metastatic lesions were seen on positron emission tomography–computed tomography. Chemotherapy and radiation therapy have not been utilized. The transfemoral amputation adds to the uniqueness of this report and is discussed with a review of the multimodality treatment toward intra-articular synovial sarcoma in prior published literature.

Background: Very high levels of ionizing radiation exposure have been associated with the development of soft-tissue sarcoma. The effects of lower levels of ionizing radiation on sarcoma development are unknown. This study addressed the role of low to moderately high levels of ionizing radiation exposure in the development of soft-tissue sarcoma. Methods: Based on the Life Span Study cohort of Japanese atomic-bomb survivors, 80,180 individuals were prospectively assessed for the development of primary soft-tissue sarcoma. Colon dose in gray (Gy), the excess relative risk, and the excess absolute rate per Gy absorbed ionizing radiation dose were assessed. Subject demographic, age-specific, and survival parameters were evaluated. Results: One hundred and four soft-tissue sarcomas were identified (mean colon dose = 0.18 Gy), associated with a 39% five-year survival rate. Mean ages at the time of the bombings and sarcoma diagnosis were 26.8 and 63.6 years, respectively. A linear dose-response model with an excess relative risk of 1.01 per Gy (95% confidence interval [CI]: 0.13 to 2.46; p = 0.019) and an excess absolute risk per Gy of 4.3 per 100,000 persons per year (95% CI: 1.1 to 8.9; p = 0.001) were noted in the development of soft-tissue sarcoma. Conclusions: This is one of the largest and longest studies (fifty-six years from the time of exposure to the time of follow-up) to assess ionizing radiation effects on the development of soft-tissue sarcoma. This is the first study to suggest that lower levels of ionizing radiation may be associated with the development of soft-tissue sarcoma, with exposure of 1 Gy doubling the risk of soft-tissue sarcoma development (linear dose-response). The five-year survival rate of patients with soft-tissue sarcoma in this population was much lower than that reported elsewhere. Level of Evidence: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

The use of staging imaging modalities with increased sensitivity has led to an increase in the incidence of detection of simultaneous malignancies. These cases require careful evaluation and discussion in a multidisciplinary setting to establish a treatment plan that optimizes the outcome with respect to each malignancy, particularly when treatment modalities overlap. We report a case of a patient diagnosed with axillary nodal diffuse large B-cell lymphoma (DLBCL) in a community hospital where staging workup also revealed synchronous bilateral breast carcinomas. To our knowledge, this is only the second case report of a patient with three synchronous primary malignancies: bilateral breast carcinomas and axillary DLBCL. The only other similar case report had no role for radiation or chemotherapy in the management of the indolent follicular lymphoma.

The purpose of this article is to report on the evaluation of vague abdominal pain and anemia in the deployed military environment resulting in the diagnosis of a giant gastric ulcer. This patient's abdominal pain was initially thought to be attributable to a lower digestive tract process and her anemia was insidious in onset but progressive. A computed tomography examination was obtained. Circumferential gastric wall thickening, more prominent posteriorly with ulceration, adjacent inflammation, and perigastric lymphadenopathy suspicious for a malignancy or a giant gastric ulcer was identified. Referral and medical evacuation to a tertiary care facility out of the deployed setting resulted in an endoscopy showing a giant gastric ulcer with no evidence of malignancy. Prompt evaluation of the patient with the most expeditious radiologic imaging modality available at hand, rather than delayed sequential evaluation, revealed an uncommon finding and conceivably saved this patient's life. Close cooperation among appropriate specialists in the deployed setting resulted in an optimal outcome in a suboptimal environment.

To report on a suspected case of idiopathic radiation recall dermatitis in an individual nine months after radiation and chemotherapy treatment of squamous cell carcinoma of the right tonsil. Radiation recall dermatitis is the development of a reaction in a previously irradiated area of skin after the administration of an aggravating medication. A review of the literature revealed several cases of radiation recall dermatitis that occur following radiation therapy and the institution of chemotherapy. Other medications have also been implicated in radiation recall dermatitis; however, this patient has not started any new medications since completion of his combined therapy. The patient developed this skin reaction in a distribution pattern identical to the area that received the highest radiation dose suggesting a possible link between radiation recall dermatitis and radiation dose. Radiation recall dermatitis is a reaction that is typically seen shortly after the reinstitution of chemotherapy during radiation therapy. This case illustrates that other medical etiologies are possible and suggests a relationship between radiation recall dermatitis and the total radiation dose an area receives.

Background: Radiation-induced bone sarcoma has been associated with high doses of ionizing radiation from therapeutic or occupation-related exposures. However, the development of bone sarcoma following exposure to lower doses of ionizing radiation remains speculative. Methods: A cohort analysis based on the Life Span Study (n = 120,321) was performed to assess the development of bone sarcoma in atomic-bomb survivors of Hiroshima and Nagasaki followed from 1958 to 2001. The excess relative risk per gray of ionizing radiation absorbed by the bone marrow was estimated. Additional subject demographic, survival, and clinical factors were evaluated. Results: Nineteen cases of bone sarcoma (in eleven males and eight females) were identified among the 80,181 subjects who met the inclusion criteria, corresponding to an incidence of 0.9 per 100,000 person-years. The mean ages at the time of the bombing and at diagnosis were 32.4 and 61.6 years, respectively. The mean bone marrow dose was 0.43 Gy. Osteosarcoma was the most commonly identified bone sarcoma. The most common bone sarcoma site was the pelvis. The overall unadjusted five-year survival rate was 25%. A dose threshold was found at 0.85 Gy (95% confidence interval, 0.12 to 1.85 Gy), with a linear dose-response association above this threshold. The linear slope equaled an excess relative risk of 7.5 per Gy (95% confidence interval, 1.34 to 23.14 per Gy) in excess of 0.85 Gy. Conclusions: On the basis of what we believe is one of the longest and largest prospective studies assessing the development of bone sarcoma in individuals exposed to ionizing radiation, it appears that the development of radiation-induced bone sarcoma may be associated with exposure to much lower doses of ionizing radiation than have previously been reported. Such new insights may potentially improve bone sarcoma prevention measures and broaden our understanding of the role of ionizing radiation from various sources on the development of malignant tumors. This study stresses the need to become increasingly aware of the various health risks that may be attributable to even low levels of ionizing radiation exposure. Level of Evidence: Prognostic Level I. See Instructions to Authors for a complete description of levels of evidence.

The aim of this paper is to report on the challenges associated with identifying disease recurrence following combined modality therapy (CMT) for primary lymphoma of the tibia in which an intramedullary nail has been placed. A patient with primary bone lymphoma (PBL) was treated with CMT (chemotherapy and radiation therapy). After a complete response, he has been followed for eighteen months by physical exam and radiographic imaging. Despite persistent increased tracer accumulation at the original site, he has no proven recurrence. Literature review showed a small number of retrospective, single institution reviews detailing clinical experience and expected outcome in patients treated with PBL limited to one bony site of disease. PBL presents a treatment challenge, particularly when a weight-bearing long bone is diffusely involved and followup is complicated after placement of stabilizing hardware. Close coordination of the oncology team and diagnostic radiology is required to ensure optimal outcome.

Purpose. There is evidence in the literature of increased maternal radiosensitivity during pregnancy. Materials and Methods. We tested this hypothesis using information from the atomic-bomb survivor cohort, that is, the Adult Health Study database at the Radiation Effects Research Foundation, which contains data from a cohort of women who were pregnant at the time of the bombings of Hiroshima and Nagasaki. Previous evaluation has demonstrated long-term radiation dose-response effects. Results/Conclusions. Data on approximately 250 women were available to assess dose-response rates for serum cholesterol, white blood cell count, erythrocyte sedimentation rate, and serum hemoglobin, and on approximately 85 women for stable chromosome aberrations, glycophorin A locus mutations, and naïve CD4 T-cell counts. Although there is no statistically significant evidence of increased radiosensitivity in pregnant women, the increased slope of the linear trend line in the third trimester with respect to stable chromosome aberrations is suggestive of an increased radiosensitivity.

Hemangiopericytoma is a rare vascular malignancy, comprising approximately 1% of all vascular neoplasms, and arises from the pericytes of Zimmerman.1 It was first described by Stout in 1949.2 The most common sites of presentation are the lower extremity, axilla, pelvis, retroperitoneum, and head and neck.3,4 Most patients present with a mass or localized pain. The lesions are histologically similar to solitary fibrous tumors, and because of this similarity, previous work on the identification and appropriate therapy for this rare malignancy is complicated by the likely inclusion of perhaps a more aggressive sarcoma in retrospective reviews.5 Management of these tumors is best planned in a multidisciplinary arena with orthopedic oncologists

Background and purpose Chest wall recurrences of breast cancer are a therapeutic challenge and durable local control is difficult to achieve. Our objective was to determine the local progression free survival (LPFS) and toxicity of thermochemoradiotherapy (ThChRT) for chest wall recurrence. Methods Twenty-seven patients received ThChRT for chest wall failure from 2/1995 to 6/2007 and make up this retrospective series. All received concurrent superficial hyperthermia twice weekly (median 8 sessions), chemotherapy (capecitabine in 21, vinorelbine in 2, and paclitaxel in 4), and radiation (median 45Gy). Patients were followed up every 1.5–3months and responses were graded with RECIST criteria and toxicities with the NCI CTC v4.0. Results Twenty-three (85%) patients were previously irradiated (median 60.4Gy) and 22 (81%) patients received prior chemotherapy. Median follow-up was 11months. Complete response (CR) was achieved in 16/20 (80%) of patients with follow-up data, and 1year LPFS was 76%. Overall survival was 23months for patients with CR, and 5.4months in patients achieving a partial response (PR) ( p =0.01). Twenty-two patients experienced acute grade 1/2 treatment related toxicities, primarily moist desquamation. Two patients experienced 3rd degree burns; all resolved with conservative measures. Conclusions ThChRT offers durable palliation and prolonged LPFS with tolerable acute toxicity, especially if CR is achieved.

In ideal circumstances, the fractionation schedule of radiotherapy should match the fractionation sensitivity of the tumor relative to the nearby normal tissues. A number of recent publications have suggested that the alpha-beta ratio (alpha/beta) for prostate is low, in the range of 1 to 3 Gy. If alpha/beta is truly low, then hypofractionated schedules using fewer, larger fractions should improve the therapeutic ratio. This critical review examines the clinical experience with hypofractionation. Several prospective trials indicate that toxicity is limited with sophisticated dose delivery and compact clinical target volume to planning target volume margins, but the single-arm nature of these trials precludes definitive statements on efficacy. Several large randomized trials comparing conventional fractionation to hypofractionation are ongoing and are described. Until these trials are completed and the results submitted for rigorous peer review, the notion that alpha/beta for prostate cancer is low remains an unconfirmed hypothesis.

Purpose: To create, on the basis of available data, a mathematical model to describe the tumor stage- and field size-dependent risks/benefits of postoperative radiotherapy (PORT) for non–small-cell lung cancer (NSCLC), and to assess whether this simple model can accurately describe the reported changes in overall survival. Methods and Materials: The increase in overall survival afforded by PORT is assumed equal to the increase in cancer-specific survival minus the rate of RT-induced mortality. The increase in cancer-specific survival is the product of the probabilities of (residual local disease) × (sterilization of residual disease with PORT) × (absence of metastatic disease). Data were extracted from the literature to estimate these probabilities. Different models were considered to relate the RT-induced mortality to field size. Results: The rate of RT-induced mortality seems to be proportional to the cube of the field size. When these mortality rates are included in the model, the predicted changes in overall survival approximate the literature values. Conclusion: Clinical data can be explained by a simple model that suggests that RT-induced mortality is strongly dependent on field size and at least partly offsets the benefit afforded by PORT. Smaller RT fields, tailored to treat the areas most at risk for recurrence, provide the highest therapeutic ratio. The data used do not reflect the impact of chemotherapy, which will reduce the rate of distant metastases and enhance the efficacy of RT.