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Background The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high‐and low‐risk patients with LA‐NPC. Methods Data from 472 LA‐NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram‐defined high‐ and low‐risk groups. Additionally, acute toxicities were evaluated comparatively between the high‐ and low‐CCD groups. Results After matching, there was no difference between different CCD groups for all patients in terms of 3‐year overall survival (OS), distant metastasis‐free survival (DMFS), locoregional recurrence‐free survival (LRRFS), or progression‐free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post‐IC EBV DNA, post‐IC primary gross tumor and lymph node volumes obtained a C‐index of 0.674. The high‐risk group determined by the nomogram had poorer 3‐year PFS, OS, DMFS, and LRRFS than the low‐risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3‐year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high‐risk group but not in the low‐risk group. Moreover, the high CCD increased treatment‐related acute toxicities. Conclusions A high CCD was associated with better 3‐year PFS and DMFS rates than a low dose for high‐risk patients but could not produce a survival benefit for low‐risk patients.

Background To ascertain if concurrent chemotherapy (CCT) benefits people with stage II nasopharyngeal carcinoma (NPC) treated with two‐dimensional radiotherapy (2DRT) or intensity‐modulated radiotherapy (IMRT). Methods A total of 4157 patients diagnosed with stage II NPC were evaluated. Patients received radiotherapy (RT) with/without CCT. Patients were divided into 2DRT and IMRT subgroups. After propensity score matching, the role of CCT was explored in these two subgroups. Overall survival (OS) was the primary endpoint and progression‐free survival (PFS), locoregional relapse‐free survival (LRFS) and distant metastasis‐free survival (DMFS) were secondary endpoints. Results In the 2DRT subgroup, CCT addition to RT benefited cases with T1N1/T2N1 in OS, PFS and LRFS (P, In this study, we explored if concurrent chemotherapy (CCT) benefits people with stage II nasopharyngeal carcinoma (NPC) treated with two‐dimensional radiotherapy (2DRT) or intensity‐modulated radiotherapy (IMRT).

Background The tumor–node–metastasis (TNM) staging system does not perform well for guiding individualized induction or adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We attempted to externally validate the Pan’s nomogram, developed based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system, for patients with locoregionally advanced disease. In addition, we investigated the reliability of Pan’s nomogram for selection of participants in future clinical trials. Methods This study included 535 patients with locoregionally advanced NPC who were treated between March 2007 and January 2012. The 5-year overall survival (OS) rates were calculated using the Kaplan–Meier method and compared with predicted outcomes. The calibration was tested using calibration plots and the Hosmer–Lemeshow test. Discrimination ability, which was assessed using the concordance index, as compared with other predictors. Results Pan’s nomogram was observed to underestimate the 5-year OS of the entire cohort by 8.65% [95% confidence interval (CI) − 9.70 to − 7.60%, P

We investigated which prognostic factor could improve survival for esophageal cancer patients who received definite concurrent chemoradiation (CCRT). Eighty patients with age ≥18, Karnofsky Performance Scale (KPS) ≥ 60, and clinical stage T1-4N0-3M0 esophageal squamous cell carcinoma were enrolled from July 2004 to December 2015. They underwent definite intensity-modulated radiotherapy (IMRT) with or without simultaneous integrated boost to the primary tumor, and reception of concurrent chemotherapy ≥ 1 cycle. The primary endpoints were overall survival (OS), locoregional progression-free survival (LRPFS) and distant metastasis-free survival (DMFS). The median follow-up duration for alive patients was 21.5 months. The rates of 2-, 3- and 5-year OS/LRPFS/DMFS were 23.8%/53.5%/49.3%, 19.1%/44.6%/49.3%, and 13.0%/44.6%/43.9%, respectively. Only the non-clinical complete response (non-cCR) after CCRT was an independent poor prognostic factor in OS (HR 3.101, 95% CI 1.535–6.265, p = 0.0016). Radiation dose >50.4 Gy and chemotherapy ≥4 cycles significantly predicted better LRPFS (p = 0.0361 and 0.0163, respectively). Poorly differentiated tumor and stage III disease have poor DMFS (p = 0.0336 and 0.0411, respectively), and chemotherapy ≥ 4 cycles was a better predictor (p = 0.0004). In subgroup analysis, patients who received radiation dose ≤50.4 Gy with concurrent chemotherapy ≥4 cycles had the best survival outcome with 1-, 2-, 3- and 5-year survival rates of 73.7%, 39.4%, 31.5% and 17.5%, respectively. In conclusion, definite radiotherapy with concurrent chemotherapy ≥4 cycles improved the survival for patients with inoperable or locally-advanced esophageal squamous cell carcinoma. Keywords: Chemoradiotherapy, Esophageal neoplasms, Squamous cell carcinoma

Background The purpose of this study was to compare the long-term survivals between altered fractionated and conventional fractionated radiotherapy with the same concurrent chemoradiotherapy (concurrent CRT) for patients with advanced nasopharyngeal carcinoma (NPC). Methods We retrospectively reviewed 203 patients with NPC who received radiotherapy (RT) by either a conventional fractionated (70-74 Gy/35-37 fractions/7-8 weeks) or altered fractionated (72-75 Gy/45 fractions/6 weeks) schedule plus the same concurrent CRT. Results The patient characteristics between conventional fractionated and altered fractionated groups showed similar distribution. The 5-year rates of nasopharyngeal failure-free, neck failure-free, and distant metastasis failure-free survival between conventional fractionated and altered fractionated groups were 88% versus 86% (P = .7781), 95% versus 93% (P = .4176), and 76% versus 73% (P = .4029), respectively. The overall survival (OS; 5-year rates were 64% versus 62%; P = .4812) and progression-free survival (PFS; 5-year rates were 67% versus 63%; P = .3829) rates also showed no significant differences. The acute and late toxicities were similar between both groups. Conclusion Altered fractionated and conventional fractionated RT achieved similar survival outcome when concurrent CRT strategy was used for advanced NPC.

Background This study assessed outcomes of patients with hypopharyngeal carcinoma treated with organ-preservation therapy utilizing intensity-modulated radiation therapy (IMRT). Methods The medical records of 98 patients treated with definitive IMRT +/- chemotherapy from 2001 to 2013 for nonmetastatic hypopharyngeal cancer were retrospectively reviewed. Results Patients were treated to doses of 66 to 72 Gy. Eighty-three patients (85%) received chemotherapy. With median follow-up of 35 months, 2-year overall survival (OS), locoregional control, progression-free survival (PFS), and laryngectomy-free survival rates were 74%, 77%, 67%, and 65%, respectively. Functional laryngeal preservation rate was 76% at 2 years. N3 disease correlated with worse OS (p < .01). Concurrent chemotherapy correlated with improved locoregional control (p = .03) and complete response to induction chemotherapy correlated with improved OS and PFS (p = .02). Actuarial 2-year and 5-year grade 3 treatment toxicities were 17% and 21%, respectively. Conclusion Favorable disease outcomes and functional laryngeal preservation rates can be achieved with IMRT for patients with hypopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Background and Aim Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC. Methods Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field. Results In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6–62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred. Conclusions The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy.

Cancer incidence rates in the UK have increased by more than a third over the last four decades, so the likelihood of requiring concurrent chemotherapy and clozapine is increasing. In this situation clinicians are faced with a clinical conundrum: to stop clozapine and risk a psychotic relapse, or to continue clozapine and risk a potentially fatal agranulocytosis. This case report describes how a multidisciplinary team (MDT) worked together to balance the mental and physical health needs of a patient.

The objective of this study was to investigate the correlation of pretreatment and posttreatment measurements as the mean apparent diffusion coefficient (ADCmean) by diffusion-weighted magnetic resonance imaging (DWI) findings with prognostic factors in patients with squamous cell carcinoma (SCC) of primary cervical cancer. The pretreatment and posttreatment ADCmean of the primary tumor were examined for their correlations with the prognosis in 69 patients with SCC of primary cervical cancer by radiotherapy (RT) with or without concurrent chemotherapy (CCRT). The median disease-free survival (DFS) and overall survival (OS) times of patients were 20.97 and 23.47 months (follow-up periods for DFS and OS: 1–72 and 1–72 months). The DFS and OS rates of patients with low pretreatment and posttreatment ADCmean of the primary tumor were also significantly worse than those of patients exhibiting high pretreatment and posttreatment ADCmean of the primary tumor (DFS; P = 0.0130 and P

In this case report, we present the history and treatment of a 70-year-old man with synchronous bilateral non-small-cell lung cancers with proton-beam radiation. Surgical treatment was not feasible and optimized photon intensity-modulated radiotherapy (IMRT) to the primary tumors would have resulted in unacceptably high normal-tissue exposures. Proton-beam radiation enabled radiation dose escalation and concurrent chemotherapy while maintaining normal-tissue tolerance.

Introduction The purpose of this study is to assess the efficacy and toxicity using once-daily reirradiation for patients with rectal cancer having received previous pelvic radiotherapy. Method Between June 1997 and June 2008, 56 patients were identified having received previous pelvic radiotherapy and received reirradiation for rectal cancer. Reirradiation intent was palliative in 43 patients, and preoperative/postoperative in 13 patients. Eighty per cent of patients received concurrent chemotherapy (n = 45). Results The median dose-fractionation reirradiation schedule was 39.6 Gy in 22 fractions once daily (range 20–39.6 Gy), and the median cumulative radiation dose was 87.3 Gy. Seven patients experienced a grade 3 acute toxicity, with no grade 4 event. Fifty-one patients (91%) completed the treatment and five patients required a treatment break. The overall symptomatic response rate was 88% at three months post-reirradiation. There was one late effect of skin ulceration among patients reirradiated palliatively. Median overall survival was 39 months in patients undergoing radical surgery versus 15 months in patients reirradiated palliatively (P

BACKGROUND We sought here to improve the toxicity of conventional concurrent chemoradiation therapy for stage III non-small cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. We report early results of a phase II study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival.

Breast cancer relapse remains a common cause of morbidity and mortality in patients who undergo initial treatment with surgery and with or without concurrent chemotherapy or radiation. Relapse rates remain high within the first decade after initial treatment, after which the risk of relapse decreases. While common within the first year of breast cancer diagnosis, pleural metastasis with malignant pleural effusion (MPE) after 10-12 years of a disease-free period is rare. Here, we present two uncommon cases of delayed breast cancer relapses with pleural metastasis, which caused MPEs.

SUMMARY Concurrent chemotherapy and radiation (CT/RT) for localized oesophageal cancer can cause life-threatening myelo-suppression. This non-randomized study examines 95 patients from three Australasian centres treated on the Trans-Tasman Radiation Oncology ‘definitivechemoradiation ‘ study. Duration of fluorouracil infusion and patient age were independently predictive of myelotoxicity after the first cycle of CT/RT. Overall rates of grade III and IV neutropaenia were 23% and of thrombocytopaenia 8% following the first cycle of chemotherapy. Five neutropaenic septic episodes followed the first cycle and six the second. All five patients recovered after the first cycle but there were four treatment-related deaths occurring after the second cycle of CT/RT. Recommendations are made concerning initial dosing, dose reductions and delays to minimize adverse patient outcomes from myelosuppression.

Between 1987 and 1989, 12 patients with advanced unresectable head and neck carcinoma were entered on a regimen of alternating and concurrent chemotherapy and radiotherapy. During the initial phase, cisplatin (50 mg/m2/day × 3 days) was administered 1 week and alternated with 160 cGy TID radiation week 3. This alternating schedule was repeated once for a total dose of 300 mg/m2 cisplatin and a total radiation dose of 4,800 cGy. Week 9, concurrent cisplatin (20 mg/m2/day × 5 days) was administered with 200 cGy BID radiation to boost ports. In spite of the alternating schedule, acute toxicity from 160 cGy TID was severe and delays secondary to mucositis increased the average duration of therapy to 11 weeks. Unexpected chronic toxicity included 2 of 12 patients with swallowing difficulty due to a sensory neuropathy which was likely a combined modality effect. This had not been reported in previous combined modality studies. A complete response was achieved in 5 of 12 patients and a partial response in 7 of 12 patients. Overall median survival was 17 months. Although the combination of cisplatin and accelerated radiation given in the above dose schedule induced a complete or partial response in all patients, severe toxicity and lack of survival benefit discourage further use of this regimen. © 1993 Wiley-Liss, Inc.

Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-killmore » rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.« less

Purpose: The purpose of this study is to present a method for evaluating the response to treatment using a commercially available deformable image registration software package (Velocity Medical Systems) and repeat PET/CT imaging. This technique can be used to identify volumes that are risk for tumor recurrence. Methods: Response to treatment was evaluated using PET/CT images acquired prior-to and post-treatment for radiation therapy patients treated with concurrent chemotherapy. Velocity (Version 3.0.1) was used to deform the initial PET/CT to the post treatment PET/CT. The post-treatment PET images were then subtracted from the pre-treatment PET images. The resulting re-sampled image is a three-dimensional SUV difference map that shows pixels with increasing SUV values. SUV values increases greater than 2.5 in the post treatment images were identified for additional follow-up. Results: A total of 5 Lung patients were analyzed as part of this study. One lung patient in the cohort had an SUV increase of +3.28 that was identified using the SUV difference map. This volume of increased uptake was located outside the treatment field and adjacent to the 35 Gy isodose line. The remaining four patients all had SUV decreases inside the planning target volume, and no unexpected areas of increase outside the irradiated volumes. All five patients were analyzed using standard tools inside the Velocity application. Conclusion: The response to treatment can easily be measured using serial PET/CT images and a commercially available deformable image registration. This provides both the radiation oncologists and medical oncologists with a quantitative assessment of their treatment to use in patient follow-up.

Historically, RT fields/doses were selected based on clinical experience and intuition. Clinicians generally recognized the imprecision of these empiric guidelines, as they did not reflect the underlying three‐dimensional anatomy,physiology, and dosimetry. A great promise afforded by 3D imaging was an improved quantitative relationship between 3D doses/volumes and outcomes. When 3D dosimetric information became more widely available (late 80s–early 90s), 3D guidelines were needed. In 1991, multiple investigators pooled the available, albeit sometimes limited, information regarding leading to the often‐quoted “Emami paper” (IJROBP 1991). During the last 17 years, additional 3D dose/volume/outcome data has become available. A central goal of QUANTEC is to summarize this information in a clinically useful manner. For each organ, the literature providing meaningful dose/volume/outcome data is reviewed. Clinical/treatment variables that may impact the application of the data is discussed. Where available, NTCP‐model parameters are provided. We hope this information will improve patient care by providing clinicians and treatment planners with the tools necessary to determine the “optimal” 3D dose distribution for each individual case. Nevertheless, the information provided herein is not ideal, and care must be taken to apply it correctly. Unfortunately, the data are incomplete for essentially almost every organ. The user must recognize the limitations inherent in extracting/pooling literature data. For some complications, some studies summarize their findings in terms of models that can be used to estimate risk. Extreme care should be taken when such models are applied clinically, especially when clinical dose/volume parameters are beyond the range used to generate the model. Models that rely on DVH data discard all spatial information (and hence inherently assume that all regions of an organ are functionally equally important), and often do not consider variations in fraction size (a particular concern with the increasing use of hypo‐fractionated schedules). Similarly, the increasing use of RT combined with concurrent chemotherapy, with rapidly evolving drugs/doses, questions the validity of historic data to modern times. For essentially all patients with curative cancers, a marginal miss is a more serious complication than is a normal tissue injury. Care must be taken not to compromise target coverage to reduce the normal tissue risks. A clinical balance is needed. Further, palliation in patients with recurrent/metastatic/incurable disease, with limited expected survival, often requires one to exceed “tolerances”, as concern for late effects may not be applicable (e.g. RT fields for locally advanced lungcancer may include large volumes of lung and heart and withholding RT due to the risk of pericarditis, or pneumonitis, may not be “therapeutically rational”). These concerns are most applicable to our youngest generation of recently‐trained radiation oncologists. Such individuals have become accustomed to having 3D dosimetric information available for every case, and rely on such data for many of their clinical decisions. These physicians may be uncomfortable in clinical settings wherein large radiation fields need to be applied in a relatively rapid fashion (i.e. without 3D dosimetry) in order to provide effective palliation.

Purpose: To assess the changes in tumor mass and volume for NSCLC patients treated with either protons or IMRT. Methods: Analyses were done on the T50 phase from weekly 4DCTs of patients with stage 3 NSCCLC treated on an IRB approved trial comparing IMRT with passively scattered protons. Patients received either 74 GY or 66 Gy in 2 Gy fractions with concurrent chemotherapy. We performed deformable registration to segment the GTV on each CT. The deformable registration process was 1) rigid registration to determine the region of the GTV 2) deformation of the contours from the planning CT 3) thresholding to account for cavities formed inside the GTV. The resultant contours were used to determine volume and mass, as determined from the TPSs CT‐to‐density curve, change over course of treatment. Results: We analyzed 48 patients 30 were treated with IMRT and 18 with protons. The ratio of GTV volume and mass between the final week CT and planning CT were 0.80 ± .21 % and 0.77 ± 0.25% for IMRT and 0.71 ± 0.21% and 0.66 ± 0.24% for protons. Conclusion: We found that tumors shrank 20‐30% when treated with concurrent chemo‐radiotherapy at 2 Gy/fraction. In addition we noted that the remaining tumor, on average, had a lower density at the end of treatment. A difference was noted between protons and IMRT but was not statistically significant. This work was, in part, funded by the National Cancer Institute.

Using easily understood language suitable for non‐biologists, this presentation will discuss the biological underpinnings, clinical significance and research directions for two increasingly important techniques in radiation oncology: the use of concurrent chemotherapy with radiation to achieve tumor sensitization; and the use of molecular imaging for the detection, characterization, treatment planning, and ultimately, the eradication of especially resistant types of cells in tumors. Special emphasis will be place on discussing methodology, strategies and clinical goals discussed by the other speakers in this educational session. Learning Objectives: 1. Better understand why chemotherapy is often given concurrently with radiotherapy as a means of producing tumor radiosensitization, based on our growing knowledge of molecular, cellular and tumor biology. 2. Describe the biological basis for molecular imaging, how it can be used for radiotherapytreatment planning purposes, and how it can facilitate the detection, characterization and ultimately, the eradication, of tumors containing therapy‐resistant cell populations. 3. Evaluate different techniques used to study drug‐radiation interactions and tumor resistance, and how these have helped guide new diagnostic and therapeutic developments.

J.W. is a 68-year-old white female who noted an "anal growth" 1 year prior to admission. She also complained of bleeding from her rectum when she was constipated. She attributed these symptoms to hemorrhoids. She noted increasing pain and more bleeding 1 month prior to admission. Locally applied hemorrhoid remedies gave her no relief. She was then admitted to a hospital where a biopsy of the anal mass was performed, and then referred to Rush-Presbyterian-St. Luke's Medical Center. On physical examination the patient was noted to be obese. There was no inguinal lymphadenopathy. There were no abdominal masses or hepatosplenomegaly. Rectal examination revealed a 3 X 4 cm mass protruding from the anus. Examination and protoscopy done under anesthesia revealed this mass to be approximately 4 X 5 cm and arising from the proximal anal canal. The mass was freely moveable and bled spontaneously when manipulated. Pelvic examination revealed a normal uterus and adnexa with no obvious tumor involvement of the vagina. Proctoscopic examination revealed no tumor proximal to the lesion described. Further evaluation included a liver-spleen scan that was negative for metastatic disease and intravenous pyelogram that showed no lesions. A barium enema revealed only diverticula. A gallium scan showed marked uptake at the area of the anal tumor but no other lesions. The chest x-ray was within normal limits. A CT scan of the abdomen and pelvis revealed no masses or lymphadenopathy. The CEA was 1.3 ng/ml. The patient underwent concomitant radiation therapy and chemotherapy. Over a 4-week period the patient received 5000 rads to the anal region. In addition, during the first week of radiation therapy and the fourth week of radiation therapy, the patient received 5-fluorouracil, 800 mg/m2 by continuous infusion for 5 days. In addition, the patient received mitomycin C, 15 mg/m2 on the first day of the first week of chemotherapy and the first day of the last week of chemotherapy. During the treatment period, the patient had mild diarrhea, perineal desquamation, and mild ulceration at the site of the anal tumor. During the third week of treatment, the patient had a white blood cell count nadir of 2800 and a platelet count of 86,000 per cubic millimeter. Her symptoms were managed with local emolients and antidiarrheal medications.(ABSTRACT TRUNCATED AT 400 WORDS)