Indications and Parameters Around Postoperative Radiation Therapy for Lung Cancer.

Patients with locally advanced resected non-small-cell lung cancer present a high risk of relapse. Although adjuvant platinum-based chemotherapy has become the standard of care, the role of postoperative radiation therapy (PORT) has been controversial for years. In patients with incomplete resection, PORT should be proposed, on the basis of a strong consensus, despite the absence of randomized evidence. In patients with completely resected (R0) non-small-cell lung cancer, a meta-analysis showed poorer outcomes after PORT in the absence of mediastinal involvement (pN0 and pN1). In patients with pN2, the role of PORT was less clear and required further research. The meta-analysis included trials using older radiation techniques and poorer quality of surgery according to today's standards, and selection of patients was not positron emission tomography-based. Newer retrospective and nonrandomized studies and subgroup analyses of randomized trials evaluating adjuvant chemotherapy suggested a survival benefit of PORT in patients with pN2 R0. Two recent randomized trials (Lung ART and PORT-C) evaluating conformal PORT versus no PORT retrieved no disease-free survival advantage for stage IIIA-N2 patients, even if mediastinal relapse was significantly decreased with PORT. PORT had no effect on survival, possibly given the high rate of distant relapse and risk of additional cardiopulmonary toxicity. Ongoing and future analyses are planned in Lung ART to identify patients for whom PORT could be recommended. Incorporation of newer systemic treatments (immune checkpoint inhibitors or targeted therapy in oncogene-addicted patients) is underway in the neoadjuvant and/or adjuvant setting. Better identification of patients at a high risk of disease recurrence, with analysis of circulating tumor DNA, on the basis of the detection of postsurgical minimal (or molecular) residual disease is warranted in future studies.

Quality of Life: A Prospective Randomized Trial of Palliative Volumetric Arc Therapy Versus 3-Dimensional Conventional Radiation Therapy.

PURPOSE: Volumetric arc therapy (VMAT) is a radiation therapy (RT) technique that spares normal tissues from high and intermediate RT doses but increases the volume of tissues receiving low doses of RT compared with 3-dimensional conformal RT (3DCRT). We hypothesized that palliative VMAT would reduce the detriment to patient quality of life (QOL) compared with palliative 3DCRT. METHODS AND MATERIALS: This phase 2 trial randomized patients to palliative RT using VMAT or 3DCRT to 1 painful site of metastatic disease in the trunk. Treating physicians could choose 8 Gy in 1 fraction or 20 Gy in 5 fractions to stratify randomization. The primary endpoint was the change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30) global health status QOL subscale at 1 week after RT. Repeated measures analysis of variance was used to assess the relationship of patient QOL over time with other factors. RESULTS: From July 2014 to November 2017, 37 patients who underwent 3DCRT and 32 patients who underwent VMAT were randomized into the study. Median overall survival was 9 months. Overall pain responses to RT were equivalent (P = .53) between the techniques. Patient compliance in returning QOL questionnaires was 94%, 81%, and 69% at baseline, 1 week after RT, and 1 month after RT, respectively. At 1 week after RT, change in global QOL was not significantly (P = .31) different between VMAT versus 3DCRT. At 4 weeks after RT, VMAT induced significantly (P = .049) less global QOL deterioration than 3DCRT did. Patients who underwent VMAT maintained better physical (P = .012), role (P = .041), and social (P = .025) functioning, but they reported more diarrhea symptoms (P = .017) than in the 3DCRT group. CONCLUSIONS: Palliative VMAT and 3DCRT did not differ in their ability to control pain; however, palliative VMAT induced fewer QOL detriments than 3DCRT did at 4 weeks after RT.

Accelerated partial breast irradiation with 3-dimensional conformal and image-guided intensity-modulated radiotherapy following breast conserving surgery - 7-Year results of a phase II trial.

PURPOSE: To present the 7-year results of accelerated partial breast irradiation (APBI) using three-dimensional conformal (3D-CRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS). PATIENTS AND METHODS: Between 2006 and 2014, 104 patients were treated with APBI given by means of 3D-CRT using 3-5 non-coplanar, isocentric wedged fields, or IG-IMRT using kV-CBCT. The total dose of APBI was 36.9 Gy (9 × 4.1 Gy) using twice-a-day fractionation. Survival results, side effects and cosmetic results were assessed. RESULTS: At a median follow-up of 90 months three (2.9%) local recurrences, one (0.9%) regional recurrence and two (1.9%) distant metastases were observed. The 7-year local (LRFS), recurrence free survival was 98.9%. The 7-year disease-free (DFS), metastases free (MFS) and overall survival (OS) was 94.8%, 97.9% and 94.8%, respectively. Late side effects included G1 skin toxicity in 15 (14.4%), G1, G2, and G3 fibrosis in 26 (25%), 3 (2.9%) and 1 (0.9%) patients respectively. Asymptomatic (G1) fat necrosis occurred in 10 (9.6%) patients. No ≥ G2 or higher late side effects occurred with IMRT. The rate of excellent/good and fair/poor cosmetic results was 93.2% and 6.8%, respectively. CONCLUSION: 7-year results of APBI with 3D-CRT and IG-IMRT are encouraging. Toxicity profile and local tumor control are comparable to other series using multicatheter interstitial brachytherapy. Therefore, these external beam APBI techniques are valid alternatives to whole breast irradiation and brachytherapy based APBI.

Intensity-modulated radiation therapy versus three-dimensional conformal radiotherapy in head and neck squamous cell carcinoma: long-term and mature outcomes of a prospective randomized trial.

PURPOSE: To compare long-term disease-related outcomes and late radiation morbidity between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in head and neck squamous cell carcinoma (HNSCC) in the setting of a prospective randomized controlled trial. METHODS: Previously untreated patients with early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx (T1-T3, N0-N2b, M0) planned for comprehensive irradiation of primary site and bilateral neck nodes were randomly assigned to either IMRT or 3D-CRT after written informed consent. Patients were treated with 6MV photons to a total dose of 70Gy/35 fractions over 7 weeks (3D-CRT) or 66Gy/30 fractions over 6 weeks (IMRT). A sample size of 60 patients was estimated to demonstrate 35% absolute difference in the incidence of ≥grade 2 acute xerostomia between the two arms. All time-to-event outcomes were calculated from date of randomization until the defined event using the Kaplan-Meier method. RESULTS: At a median follow-up of 140 months for surviving patients, 10-year Kaplan-Meier estimates of loco-regional control (LRC); progression-free survival (PFS); and overall survival (OS) with 95% confidence interval (95%CI) were 73.6% (95%CI: 61.2-86%); 45.2% (95%CI: 32-58.4%); and 50.3% (95%CI: 37.1-63.5%) respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRC [79.2% (95%CI: 62.2-96.2%) vs 68.7% (95%CI: 51.1-86.3%), p = 0.39]; PFS [41.3% (95%CI: 22.3-60.3%) vs 48.6% (95%CI: 30.6-66.6%), p = 0.59]; or OS [44.9% (95%CI: 25.7-64.1%) vs 55.0% (95%CI: 37-73%), p = 0.49]. Significantly lesser proportion of patients in the IMRT arm experienced ≥grade 2 late xerostomia and subcutaneous fibrosis at all time-points. However, at longer follow-up, fewer patients remained evaluable for late radiation toxicity reducing statistical power and precision. CONCLUSIONS: IMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC.

Correlation between hematological parameters and outcome in patients with locally advanced cervical cancer treated by concomitant chemoradiotherapy.

BACKGROUND: Hemoglobin (Hb), white blood cell (WBC), and polymorphonuclear neutrophil (PMN) blood counts may be correlated with outcomes in patients with locally advanced cervical cancer. METHODS: Hb, WBC, and PMN counts were measured at diagnosis and during concomitant cisplatin-based chemoradiotherapy (CCRT) in a retrospective sample of 103 patients between 2010 and 2017. Red blood cell (RBC) transfusions were also recorded. The associations between hematological variables and patient overall survival (OS) and recurrence-free survival (RFS) were assessed by Cox regression models. RESULTS: The 3-year OS and RFS rates were 81.4% and 76.8%, respectively. In addition to tumor size and smoking, OS and RFS were found to be significantly associated with changes in WBC and PMN counts from the first to the last cisplatin cycle. Hb count throughout the treatment and RBC transfusions were not predictive of outcome. CONCLUSIONS: This study found no association between Hb count or RBC transfusions and outcome. The daily practice of maintaining the Hb count above 12 g/dL during CCRT should be weighed against the potential risks of transfusions. Drops in WBC and PMN counts during treatment positively impacted OS and RFS and could, therefore, serve as biomarkers during CCRT to adapt the follow-up and consider the need for adjuvant systemic treatments.

Assessment of the results and hematological side effects of 3D conformal and IMRT/ARC therapies delivered during craniospinal irradiation of childhood tumors with a follow-up period of five years.

BACKGROUND: Craniospinal irradiation (CSI) of childhood tumors with the RapidArc technique is a new method of treatment. Our objective was to compare the acute hematological toxicity pattern during 3D conformal radiotherapy with the application of the novel technique. METHODS: Data from patients treated between 2007 and 2014 were collected, and seven patients were identified in both treatment groups. After establishing a general linear model, acute blood toxicity results were obtained using SPSS software. Furthermore, the exposure dose of the organs at risk was compared. Patients were followed for a minimum of 5 years, and progression-free survival and overall survival data were assessed. RESULTS: After assessment of the laboratory parameters in the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side effects during the IMRT/ARC and 3D conformal treatments. Laboratory parameters decreased significantly compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival or overall survival, and no signs of serious organ toxicity due to irradiation were observed during the follow-up period in either of the groups. CONCLUSION: The RapidArc technique can be used safely even in the treatment of childhood tumors, as the extent of the exposure dose in normal tissues and the amount of acute hematological side effects are not higher with this technique.

Low Fraction Size Re-irradiation for Large Volume Recurrence of Glial Tumours.

The aim of the present study was to evaluate the efficacy of re-irradiation (re-RT) in patients with advanced local relapses of glial tumours and to define the factors influencing the result of the hyper-fractionated external beam therapy on progression after primary management. We have analysed the data of 55 patients with brain tumours (GBM: 28) on progression, who were re-irradiated between January 2007 and December 2018. The mean volume of the recurrent tumour was 118 cm3, and the mean planning target volume (PTV) was 316 cm3, to which 32 Gy was delivered in 20 fractions at least 7.7 months after the first radiotherapy, using 3D conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT). The median overall survival (mOS) from the re-RT was 8.4 months, and the 6-month and the 12-month OS rate was 64% and 31%, respectively. The most important factors by univariate analysis, which significantly improved the outcome of re-RT were the longer time interval between the diagnosis and second radiotherapy (p = 0.029), the lower histology grade (p = 0.034), volume of the recurrent tumour (p = 0.006) and Karnofsky performance status (KPS) (p = 0.009) at the re-irradiation. Our low fraction size re-irradiation ≥ 8 months after the first radiotherapy proved to be safe and beneficial for patients with large volume recurrent glial tumours.

Clinical outcomes following proton therapy for adult craniopharyngioma: a single-institution cohort study.

BACKGROUND: Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response. METHODS: We analyzed 14 adult patients (≥ 22 years old). All patients had gross disease at the time of radiotherapy. Five were treated for de novo disease and 9 for recurrent disease. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2-54 GyRBE). Weekly magnetic resonance imaging (MRI) helped to evaluate tumor changes during radiotherapy. RESULTS: With median clinical and radiographic follow-up of 29 and 26 months, respectively, the 3-year local control and overall survival rates were both 100%. There were no grade 3 or greater acute or late radiotherapy-related side effects. There was no radiotherapy-related vision loss or optic neuropathy. No patients required intervention or treatment replanning due to tumor changes during radiotherapy. Two patients experienced transient cyst expansion at their first post-radiotherapy MRI. Both patients were followed closely clinically and radiographically and had subsequent dramatic tumor/cyst regression, requiring no interventions. CONCLUSIONS: Our data support the safety and efficacy of proton therapy in the treatment of adult craniopharyngioma as part of primary or salvage treatment. We recommend early consideration of radiotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03224767.

Impact of Brachytherapy Boost and Dose-escalated External Beam Radiotherapy in Margin Positive Cervical Cancer Treated With Chemotherapy and Radiation.

OBJECTIVES: We examined the impact of brachytherapy boost (BB) and external beam radiotherapy (EBRT) dose-escalation on overall survival (OS) for women with cervical cancer receiving postoperative chemotherapy and radiation (CRT) for a positive margin following hysterectomy. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2015 for women with nonmetastatic squamous cell carcinoma or adenocarcinoma of the cervix who had a positive margin following hysterectomy and received postoperative CRT. Patient and treatment characteristics were assessed with multivariate logistic regression. Survival analyses were performed with univariate Cox regression and Kaplan-Meier analyses. Propensity-score weighted cohorts were generated with inverse probability of treatment weighting via generalized boosted regression modeling. RESULTS: Of 630 women receiving CRT, 331 (53%) received EBRT alone and 299 (47%) received EBRT+BB. Eighty-two percent had chemotherapy initiation within 2 weeks of radiation, suggesting concurrent delivery. Median EBRT dose was 5040 cGy. Intracavitary high-dose rate was the most common BB (67%). Inclusion of BB was more likely with larger tumor sizes (odds ratio=1.03, P=0.002). Women receiving EBRT+BB had improved OS compared to EBRT alone for both unweighted (hazard ratio [HR], 0.72; P=0.020) and propensity-score weighted cohorts (HR, 0.70; P=0.017), and this finding was consistent across multiple patient subsets. EBRT dose-escalation >5040 cGy was not found to be associated with OS (unweighted HR, 1.38; P=0.065 and weighted HR, 1.16; P=0.450). CONCLUSION: The addition of BB to standard CRT improved OS for women with cervical cancer and a positive margin after hysterectomy. No consistent survival benefit was seen to EBRT dose-escalation beyond 5040 cGy.

Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial.

BACKGROUND: Radiotherapy is the standard salvage treatment after radical prostatectomy. To date, the role of androgen deprivation therapy has not been formally shown. In this follow-up study, we aimed to update the results of the GETUG-AFU 16 trial, which assessed the efficacy of radiotherapy plus androgen suppression versus radiotherapy alone. METHODS: GETUG-AFU 16 was an open-label, multicentre, phase 3, randomised, controlled trial that enrolled men (aged ≥18 years) with Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed adenocarcinoma of the prostate (but no previous androgen suppression or pelvic radiotherapy), stage pT2, T3, or T4a (bladder neck involvement only) and pN0 or pNx according to the tumour, node, metastasis (TNM) staging system, whose prostate-specific antigen (PSA) concentration increased from 0·1 ng/mL to between 0·2 ng/mL and 2·0 ng/mL after radical prostatectomy, without evidence of clinical disease. Patients were assigned through central randomisation (1:1) to short-term androgen suppression (subcutaneous injection of 10·8 mg goserelin on the first day of irradiation and 3 months later) plus radiotherapy (3D conformal radiotherapy or intensity modulated radiotherapy of 66 Gy in 33 fractions, 5 days a week for 7 weeks) or radiotherapy alone. Randomisation was stratified using a permuted block method (block sizes of two and four) according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival in the intention-to-treat population. This post-hoc one-shot data collection done 4 years after last data cutoff included patients who were alive at the time of the primary analysis and updated long-term patient status by including dates for first local progression, metastatic disease diagnosis, or death (if any of these had occurred) or the date of the last tumour evaluation or last PSA measurement. Survival at 120 months was reported. Late serious adverse effects were assessed. This trial is registered on ClinicalTrials.gov, NCT00423475. FINDINGS: Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. At the time of data cutoff (March 12, 2019), the median follow-up was 112 months (IQR 102-123). The 120-month progression-free survival was 64% (95% CI 58-69) for patients treated with radiotherapy plus goserelin and 49% (43-54) for patients treated with radiotherapy alone (hazard ratio 0·54, 0·43-0·68; stratified log-rank test p<0·0001). Two cases of secondary cancer occurred since the primary analysis, but were not considered to be treatment related. No treatment-related deaths occurred. INTERPRETATION: The 120-month progression-free survival confirmed the results from the primary analysis. Salvage radiotherapy combined with short-term androgen suppression significantly reduced risk of biochemical or clinical progression and death compared with salvage radiotherapy alone. The results of the GETUG-AFU 16 trial confirm the efficacy of androgen suppression plus radiotherapy as salvage treatment in patients with increasing PSA concentration after radical prostatectomy for prostate cancer. FUNDING: The French Health ministry, AstraZeneca, la Ligue Contre le Cancer, and La Ligue de Haute-Savoie.

Evaluation of surgery plus postoperative radiotherapy or definitive radiotherapy in older patients with thoracic esophageal squamous cell cancer.

PURPOSE: This study investigated the outcome of elderly patients (≥65 years) with thoracic esophageal squamous cell carcinoma (TESCC) treated with esophagectomy and postoperative radiotherapy (PORT) or definitive radiotherapy (DRT). PATIENTS AND METHODS: One hundred and ninety patients (median age of 72 years) who received PORT (n = 68) or DRT (n = 122) for TESCC were analyzed. Majority of them showed locally advanced disease (T3/4: 70.5%, N+: 70.5%, Stage III: 51.6%). Compared to patients who received DRT, those who received PORT had lower Age-Adjusted Charlson Comorbidity Index (AACCI) scores (2.49 ± 0.61 vs. 3.73 ± 1.28, χ2 = 7.283; P = 0.000) and higher Karnofsky Performance Scale (KPS) (χ2 = 9.016; P = 0.003) and were of younger ages (68.90 ± 3.00 vs. 75.17 ± 5.71, χ2 = 9.925; P = 0.000). RESULTS: Overall survival (OS) was significantly higher in the PORT group (median, 61.2 months; 95% confidence interval [CI], 46.04-76.36) than in the DRT group (median, 24.37 months; 95% CI, 15.43-33.31). Multivariate analysis showed that treatment method (hazard ratio [HR]: 2.38, 95% CI, 1.46-3.90; P = 0.001), clinical T stage (HR: 0.57, 95% CI, 0.34-0.95; P = 0.031), and lymph node metastasis (HR: 0.51, 95% CI, 0.31-0.84; P = 0.008) were independent prognostic factors. Regarding subgroup analysis, OS of patients receiving PORT was significantly higher than that of DRT in the T3-4 group (HR: 2.98, 95% CI, 1.80-4.92; P = 0.000) and the N+ group (HR: 2.20, 95% CI, 1.26-3.83; P = 0.006). CONCLUSIONS: The efficacy of PORT for the treatment of elderly TESCC patients was superior to DRT. With regard to AACCI, KPS, and age, DRT is still a treatment option for elderly TESCC patients, especially for those >75 years of age.

Adjuvant volumetric modulated arc therapy compared to 3D conformal radiation therapy for newly diagnosed soft tissue sarcoma of the extremities: outcome and toxicity evaluation.

OBJECTIVE: To assess the impact of adjuvant volumetric modulated arc therapy (VMAT) compared with three-dimensional conformal radiation therapy (3DCRT) in terms of toxicity and local control (LC) in patients with soft tissue sarcoma of the extremities. METHODS: From 2004 to 2016, 109 patients were treated, initially using 3DCRT and subsequently with VMAT. Clinical outcome was evaluated by contrast-enhanced MRI, thoracic and abdominal CT 3 months after treatments and then every 6 months. Toxicity was evaluated with Common Terminology Criteria for Adverse Events scale v. 4.3. RESULTS: Patients presented Stage III soft tissue sarcoma disease (77%), localized tumor (95%) at the lower extremity (87%), adipocytic histotype (46%). Surgical resection was performed in all patients, followed by adjuvant 3DCRT in 38, and VMAT in 71. The median total dose was 66 Gy/33 fractions (range 60-70 Gy;25-35 fractions). More successful bone sparing was recorded using VMAT (p < 0.001). Median follow-up was 61 months, 93 and 58 months for 3DCRT and VMAT group, respectively. The 2- and 5 year LC were 95.3±2.1%, and 87.4±3.4% for the whole cohort, 92.0±4.5%, 82.9±6.4% for 3DCRT, 97.1±2.0%, 89.6±4.1% for VMAT (p = 0.150). On univariate and multivariate analysis the factors recorded as conditioning LC were the status of the surgical resection margins (p = 0.028) and the total dose delivered (p = 0.013). CONCLUSION: The availability of modern radiotherapy technique permit a better conformity on the target with maximum sparing of normal tissue and acceptable side-effects. VMAT is a safe and feasible treatment with limited rate of toxicity, compared to 3DCRT. Results on LC of VMAT are encouraging. ADVANCES IN KNOWLEDGE: Soft tissue sarcoma of the extremities can benefit from the use of VMAT, with a reduction of the high dose to bones to avoid radiation osteonecrosis. An adequate total dose of at least 66 Gy and a radical surgical margin allow a good local control.

Surgery or Radiotherapy of the Primary Tumor in T1-2 Head and Neck Squamous Cell Carcinoma with Resectable N3 Nodes: A Multicenter GETTEC Study.

BACKGROUND: The prognosis of advanced nodal (N3) squamous cell carcinoma of the head and neck (HNSCC) is poor. We investigated whether surgery or radiotherapy of early (T1-2) primary stage HSNCC is preferable to limit the overall morbidity after upfront neck dissection (uND) for N3 disease. METHODS: This retrospective multicentric Groupe d'Étude des Tumeurs de la Tête Et du Cou study included patients undergoing uND and surgery or radiotherapy of their primary. Prognostic factors were evaluated using propensity score matching to account for biases in performing surgery depending on primary site and stage. RESULTS: Of 189 T1-2, N3 HNSCC patients, 70 (37.0%) underwent uND: 42 with surgery of their primary and 28 with radiotherapy only. Radiotherapy alone was more frequent in patients with hypopharyngeal primaries. All local (N = 3) and regional (N = 10) relapses (included 2 locoregional relapses) occurred within the first 2 years. There were 16 distant metastatic failures. Five-year locoregional relapse and survival incidences were 15.7% and 66.5% and were similar regardless of the treatment of the primary. The overall morbidity rate was 65.2% and was similar after weighting by the inverse propensity score (p = 0.148). The only prognostic factor for morbidity was the radicality of the uND. Prolonged parenteral feeding was not more frequent in patients only irradiated to their primary (p = 0.118). Prolonged tracheostomy was more frequent after surgery of the primary. CONCLUSIONS: In patients with T1-2, N3 HNSCC undergoing uND, radiotherapy and surgery of the primary yield similar oncological outcomes. Morbidity was related to the extent of neck dissection.

Descriptive Study of Nasopharyngeal Carcinoma and Treatment Outcomes: An Eight Years Experience in Hadhramout National Cancer Centre, Yemen.

OBJECTIVE: To describe the histological patterns, and to evaluate the long-term outcomes of non surgical treatment of nasopharyngeal carcinoma (NPC) in patients registered at Hadhramout National Cancer Centre (HNCC) in Mukalla City, in Hadhramout Province, Yemen. METHODS: Non-randomized descriptive cancer registrybased study of patients with different WHO types of nasopharyngeal cancer and different non surgical treatment modality. Data was obtained from the medical records of patients seen and followed-up at HNCC. Data was collected using Can-Reg 10 computerized program and statistical analysis done using SPSS version-17 software program. RESULTS: The study included 109 patients with NPC, males were 71(65.14%) and females were 38(34.86%), with a male to female ratio of 2:1. The mean age was 43 (range10-89 years). The majority of the patients were from Hadhramout 85(77.98%), while 24(22.2%) patients were from outside Hadhramout. The most common type of NPC seen according WHO classification was type III 82(75.24%) patients, followed by type II 15(13.76%) patients, and lastly type I 12(11%). The type III tumors of nasopharynx was the predominant type seen in younger patients. Cervical nodal metastasis was found in 86(78.9%) patients, N0 neck was observed in 23(21.1%) patients. The highest annual incidence was observed in 2011 and 2012; fourteen females and 31 males. Patients who underwent curative radiotherapy were 14(12.85%), chemotherapy were 33(30.28%), and concurrent chemoradiotherapy were 62 (56.88%) as initial cancer treatment. Deaths during follow-up period due to local recurrences of NPCs after radiotherapy, chemotherapy and chemoradiotherapy were 1(0.92%), 5(4.59%), 11(10%) respectively. The period of follow-up was 72 months. Two patients were lost from follow-up. CONCLUSION: Our results reveal that WHO-NPC type III is the most common type seen in patients, and the predominant type in young males who presented from Hadhramout regions. Treatment outcome was best in irradiated group followed by chemoradiotherapy and lastly chemotherapy.

Efficacy and safety of intensity-modulated radiation therapy versus three-dimensional conformal radiation treatment for patients with gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Radiation or radiochemotherapy is a common adjuvant therapy for gastric cancer. Intensity-modulated radiation therapy (IMRT) has been demonstrated to provide better dose conformity, allowing dose escalation and/or reduction of normal tissue exposure compared with three-dimensional conformal radiation treatment (3D-CRT). However, the efficacy of IMRT and 3D-CRT in gastric cancer remains controversial. This study aimed to compare the efficacy and safety of IMRT with those of 3D-CRT in treating patients with gastric cancer through conducting a meta-analysis of 3-year survival rates [overall survival (OS) and disease-free survival (DFS)], local control rates, and toxic event rates. METHODS: Embase, PubMed, the Cochrane Library, and clinical trial databases were searched to identify the clinical trials of IMRT versus 3D-CRT for treating patients with gastric cancer. The obtained data of survival and safety were analyzed using the Stata 14.0 software. RESULTS: A total of 9 controlled clinical studies, including 516 patients with gastric cancer, met the inclusion criteria and were included in this meta-analysis. The results of the meta-analysis showed that the 3-year OS rate was slightly higher in the IMRT group than in the 3D-CRT group, without any statistical significance. The 3-year local control rate was significantly higher in the IMRT group than in the 3D-CRT group. No significant difference in the 3-year DFS rate was found between the IMRT and 3D-CRT groups. Grade 2-4 toxicities were similar between the IMRT and 3D-CRT groups. CONCLUSION: The findings suggested that IMRT might be superior to 3D-CRT in treating patients with gastric cancer in terms of local control rates without increasing toxicity.

[The efficacy and safety of high dose versus standard dose radiotherapy in concurrent chemoradiotherapy for patients with esophageal squamous cell carcinoma].

Objective: To compare the efficacy and treatment-related toxicity of high dose versus standard dose radiotherapy in concurrent chemoradiotherapy (CCRT) for patients with esophageal squamous cell carcinoma (ESCC). Methods: From 2005 to 2012, 183 pairs of patients with esophageal squamous cell carcinoma in the Fourth Hospital of Hebei Medical University were enrolled, all had undergone CCRT based on three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). A propensity score was constructed to match the cohort. The overall survival (OS), local control (LC) probability, as well as the acute and late toxicities between standard-dose and high-dose groups were compared. Results: Patients in the high-dose group had significantly better OS and LC probability compared with those in the standard-dose group: the 3-, 5- and 10-year LC rate were 60.9%, 57.6%, 52.3% versus 50.8%, 46.4%, 30.8%, respectively (P=0.032). The 3-, 5- and 10-year OS were 44.3%, 36.9% and 24.5% for high-dose group, and 31.7%, 20.6% and 14.1% for the standard-dose group, respectively(P=0.002). The incidence of acute radiation esophagitis (especially in grade 2 and 3) was 63.9% in high-dose group, which was significantly higher than that in the standard-dose group (59.6%). Severe (≥ grade 3) late-onset esophagitis was observed in neither group. The grade 4 acute esophagitis was rare. There was no significant difference in the incidence of radiation pneumonitis, gastrointestinal reactions or hematological toxicities between the two groups. Six patients in high-dose group and two patients in standard-dose group experienced ≥ grade 4 leukocytopenia, while no one experienced > grade 3 thrombocytopenia and anemia in both group. Conclusions: 60 Gy was the preferred dosage of CCRT in patients with ESCC. Compared with standard-dose, the high-dose CCRT yielded slightly increased mild to moderate acute radiation esophagitis, while life-threatening toxicities were not increased.

Intensity-modulated radiotherapy at high-volume centers improves survival in patients with esophageal adenocarcinoma receiving trimodality therapy.

The standard of care trimodality therapy for resectable locally advanced esophageal adenocarcinoma is complex and necessitates multidisciplinary care and expertise. In this work, it is hypothesized that facility clinical volume and utilization of intensity-modulated radiotherapy (IMRT) may influence outcomes. The National Cancer Data Base was queried for patients with cT1-4-N0-3 M0 esophageal adenocarcinoma undergoing trimodality therapy from 2004 to 2013 (n = 2445). All patients received chemoradiation followed by esophagectomy at a Commission on Cancer facility. The facility volume was categorized into tertiles: high-volume centers (HVCs) in the highest 25th percentile of cases per year, intermediate-volume centers (IVCs) with the next highest 25th percentile of cases, and low- and very low-volume centers (LVCs) in the lowest 50th percentile. Overall survival (OS) was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Propensity score matching to balance patient characteristics between volume centers was performed. Subgroup analysis was done comparing IMRT versus 3D conformal radiotherapy. The median follow-up was 26 months. Treatment at an HVC (hazard ratio 0.63, 95% CI 0.49-0.81, P < 0.001) was found to be independently associated with improved overall survival in multivariable analysis. Three-year OS was 58.4%, 46.2%, and 47.5% for HVCs, IVCs, and LVCs, respectively (P < 0.001). Patients at HVCs were more likely to receive IMRT over 3D chemoradiation (CRT; OR 3.45, 95% CI 2.4-5.0, P < 0.001). Patients treated using IMRT at HVCs had improved OS compared to those treated at IVCs or LVCs (HR 0.68, 95% CI 0.52-0.90, P < 0.01), while patients treated with 3D CRT at HVCs had no survival advantage over those at IVCs or LVCs (P = 0.28). Patients with locally advanced esophageal adenocarcinoma treated with IMRT and at HVCs appear to have improved survival.

Transcatheter arterial chemoembolization (TACE) combined with γ-knife compared to TACE or γ-knife alone for hepatocellular carcinoma.

To compare the clinical efficacies and adverse reactions between transcatheter arterial chemoembolization (TACE), γ-ray 3-dimensional fractionated stereotactic conformal radiotherapy (FSCR), and TACE combined with FSCR for primary hepatocellular carcinoma.The study was approved by the Institutional Review Board, and informed consent was waived due to the retrospective study design. About 121 patients met the inclusion criteria and were included in this study, from March 2008 to January 2010, in the Second Xiangya Hospital. Forty-six patients underwent TACE alone, 36 patients underwent γ-knife alone, and 39 were treated by γ-knife combined with TACE. Short-term effects, overall survival rates, adverse reactions, and survival times were compared between the 3 treatment groups.Short-term effects were observed in 41.3% of the TACE group, 33.3% of the γ-knife group, and 64.1% of the TACE combined γ-knife group (P = .020). Overall survival rates at 6,12, 18, and 24 months were 50%, 34.8%, 28.3%, and 21.7% for the TACE group, 36.1%, 30.6%, 16.7%, and 11.1% for γ-knife group, and 84.6%, 71.8%, 61.5%, and 30.8% for TACE combined γ-knife group, respectively. The differences in the overall survival rates at 6, 12, and 18 months between the 3 groups were statistically significant (P = 0), but the overall survival rates at 24 months in the 3 groups were not significantly different (P = .117). The median survival time was 7 months for the TACE group, 3 months for the γ-knife group, and 20 months for the TACE combined γ-knife group (P = 0). There were statistically significant differences (P = .010) of leukopenia between the 3 groups, and no statistically significant differences of (P > .05) thrombocytopenia, anemia, nausea, vomiting, and liver function lesions.TACE combined with γ-knife for primary hepatocellular carcinoma is superior to TACE or γ-knife alone in short-term and long-term effects. This procedure is a mild, safe, and effective treatment for primary hepatocellular carcinoma.

Comparison of intensity-modulated radiotherapy vs 3-dimensional conformal radiotherapy for patients with non-metastatic esophageal squamous cell carcinoma receiving definitive concurrent chemoradiotherapy: A population-based propensity-score-matched analysis.

Whether the survival outcome of patients with non-metastatic esophageal squamous cell carcinoma (NM-ESCC) receiving definitive concurrent chemoradiotherapy (CCRT) is better with intensity-modulated radiotherapy (IMRT) or with 3-dimensional conformal radiotherapy (3DCRT) has been debated in the literature. We designed this population-based propensity-score (PS)-matched analysis to address this question. We identified eligible patients diagnosed between 2008 and 2015 from the Taiwan Cancer Registry and constructed a PS-matched cohort (1:1 for IMRT vs 3DCRT) to balance observable potential confounders. We compared the hazard ratio (HR) of death between IMRT and 3DCRT during the entire follow-up period. We also evaluated freedom from local regional recurrence (FFLRR) and esophageal cancer-specific survival (ECSS). Sensitivity analyses (SA) were performed to examine the robustness of our findings. Our study population constituted 558 patients who were well balanced with regard to the measured covariables. The HR of death with IMRT compared to 3DCRT was 0.43 (95% confidence interval 0.35-0.52, P < .001). The results remained significant for FFLRR and ECSS. In SA, our results remained significant when additional covariables were taken into consideration. The survival outcome of patients with NM-ESCC receiving CCRT might be better with IMRT vs 3DCRT. These study results should be interpreted with caution given some possible covariates lacking in the registry. Further studies are needed to clarify this issue.

Impact of Radiation Therapy Dose Escalation on Prostate Cancer Outcomes and Toxicities.

OBJECTIVES: Freedom from biochemical failure (FFBF) is a common primary outcome of randomized-controlled trials of prostate cancer (PCa). We aimed to determine how increasing the PCa biologically equivalent dose (BED) of external radiation therapy (RT) is correlated with FFBF and overall patient outcomes: overall survival (OS), distant metastasis (DM), and cancer-specific mortality (CSM); as well as genitourinary (GU), and gastrointestinal toxicities. MATERIALS AND METHODS: We performed a meta-analysis of 6884 PCa patients from 12 randomized-controlled trials of external beam RT. Mixed effects regression models were used to estimate weighted linear relationships between BED and observed percentages of 5- and 10-year outcomes. For toxicities, a subset analysis of using 3-dimensional conformal RT (3D-CRT) versus intensity-modulated RT (IMRT) was performed. RESULTS: Increasing BED correlated with improved FFBF: 10-year absolute improvement of 9.6% and 7.2% for low-risk and intermediate-risk patients, respectively (P<0.05); but not with improvement of OS, DM, or CSM at either time point. BED escalation was not correlated with increased acute toxicities; it was correlated with increased late gastrointestinal toxicities in patients treated with 3D-CRT (1.5% increase over BED range, P<0.01). IMRT patients had significantly fewer late toxicities, despite being treated at higher BED. CONCLUSIONS: RT BED escalation has resulted in significantly improved PCa FFBF at up to 10 years; but not with improvement in OS, DM, or CSM. Thus, FFBF is a poor surrogate of overall patient outcomes for trials of RT. Late toxicities were less frequent with IMRT than with 3D-CRT, even at higher BED.