Dose-Dependent Transcriptional Response to Ionizing Radiation Is Orchestrated with DNA Repair within the Nuclear Space.

Radiation therapy is commonly used to treat glioblastoma multiforme (GBM) brain tumors. Ionizing radiation (IR) induces dose-specific variations in transcriptional programs, implicating that they are tightly regulated and critical components in the tumor response and survival. Yet, our understanding of the downstream molecular events triggered by effective vs. non-effective IR doses is limited. Herein, we report that variations in the genetic programs are positively and functionally correlated with the exposure to effective or non-effective IR doses. Genome architecture analysis revealed that gene regulation is spatially and temporally coordinated with DNA repair kinetics. The radiation-activated genes were pre-positioned in active sub-nuclear compartments and were upregulated following the DNA damage response, while the DNA repair activity shifted to the inactive heterochromatic spatial compartments. The IR dose affected the levels of DNA damage repair and transcription modulation, but not the order of the events, which was linked to their spatial nuclear positioning. Thus, the distinct coordinated temporal dynamics of DNA damage repair and transcription reprogramming in the active and inactive sub-nuclear compartments highlight the importance of high-order genome organization in synchronizing the molecular events following IR.

Pancreatic cancer outcome-local treatment with radiation using MRI-LINAC.

Introduction: Stereotactic MR-guided on-table adaptive radiotherapy (SMART) allows the precise delivery of high-dose radiation to tumors in great proximity to radiation-sensitive organs. The aim of this study is to evaluate the toxicity and clinical outcome in locally advanced or recurrent pancreatic tumors, with or without prior irradiation, treated with SMART. Methods: Patients were treated for pancreatic cancer (PC) using SMART technology to a prescribed dose of 50 Gy (BED10, 100 Gy) in five fractions, with daily on-table adaptation of treatment plan. Endpoints were acute and late toxicities, local control, local disease-free period, and overall survival. Results: A total of 54 PC patients were treated between August 2019 and September 2022, with a median follow-up of 8.9 months from SMART. The median age was 70.4 (45.2-86.9) years. A total of 40 patients had upfront inoperable PC (55% were locally advanced and 45% metastatic), and 14 had local recurrence following prior pancreatectomy (six patients also had prior adjuvant RT). Of the patients, 87% received at least one chemotherapy regimen (Oxaliplatin based, 72.2%), and 25.9% received ≥2 regimens. Except from lower CA 19-9 serum level at the time of diagnosis and 6 weeks prior to SMART in previously operated patients, there were no significant differences in baseline parameters between prior pancreatectomy and the inoperable group. On-table adaptive replanning was performed for 100% of the fractions. No patient reported grade ≥2 acute GI toxicity. All previously irradiated patients reported only low-grade toxicities during RT. A total of 48 patients (88.9%) were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for a median of 9 months (2.8-28.8); three had later local progression. Eight patients had regional or marginal recurrence. Six- and 12-month OS were 75.0% and 52.1%, respectively. Apart from mild diarrhea 1-3 months after SMART and general fatigue, there were no significant differences in toxicity and outcomes between post-pancreatectomy and inoperable groups. Conclusion: SMART allows safe delivery of an ablative dose of radiotherapy, with minimal treatment-related toxicity, even in previously resected or irradiated patients. In this real-world cohort, local control with complete response was achieved by 20% of the patients. Further studies are needed to evaluate long-term outcome and late toxicity.

Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery.

OBJECTIVE: We hypothesized that driver mutations in epidermal growth factor receptor (EGFR) are associated with decreased pathologic response to neoadjuvant chemoradiation (NA-ChRT) in locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: Patients with Stage IIB-IIIA NSCLC treated with NA-ChRT, completion surgery, and underwent molecular profile testing were identified in a lung cancer database. Pathologic response was quantified using: (i) major pathologic response (MPR), (ii) complete pathologic response (pCR), and (iii) mean residual viable tumor cells (MRTC). Two groups were formed based on the presence or absence of driver mutations. Clinical and pathological correlations between the groups were studied. RESULTS: Forty-seven patients underwent tumor molecular profile testing, NA-ChRT, and completion surgery. Compared to the no-driver mutation group, the driver mutation group had lower MPR (23% vs 71%, p = 0.003), pCR (0% vs 26%, p = 0.02), and higher MRTC (43.4% vs 15.8%, p = 0.009). Univariate analysis showed an increased MPR rate for smokers, squamous cell histology, ChRT-surgery interval >65 days, and no-driver mutations. Multivariate analysis showed that only no-driver mutations (OR 0.39, p = 0.02) remained significant for MPR. PD-L1 status did not affect MPR. At 2 years, the driver mutation group had lower rates of local control (Hazard ration [HR] 0.67, p = 0.17) and disease-free survival (HR 0.5, p = 0.001). Overall survival was similar for both groups (HR = 1.04, p = 0.86). CONCLUSION: Following 60 Gray NA-ChRT, tumors with a driver mutation had lower MPR and pCR rates than tumors without a driver mutation. PD-L1 was not associated with tumor regression. ADVANCES IN KNOWLEDGE: Patients with resectable LA-NSCLC and an EGFR driver mutation treated with neoadjuvant-ChRT and completion surgery have reduced pathologic regression, lower local control rates, and shorter disease-free survival than patients without a driver mutation. Evaluation of molecular testing should be introduced in LA-NSCLC intended for prognostication and treatment decisions.

Deep inspiratory breath hold assisted by continuous positive airway pressure ventilation for lung stereotactic body radiotherapy.

PURPOSE: Continuous positive airway pressure (CPAP) ventilation hyperinflates the lungs and reduces diaphragmatic motion. We hypothesized that CPAP could be safely combined with deep inspiratory breath hold (CPAP-DIBH) during lung stereotactic radiotherapy (SBRT). MATERIAL AND METHODS: Patients with stage-1 lung cancer or lung metastasis treated with CPAP-DIBH SBRT between 3/2017-5/2021 were analyzed retrospectively. Patient characteristics, treatment parameters, duration of breath holds in all sessions and tolerance to CPAP-DIBH were recorded. Local control (LC) was assessed from CT or PET-CT imaging. The distances between the tumor and mediastinal organs at risk (OAR) in centrally located tumors using either free breathing (FB) or CPAP-DIBH were compared. Toxicity was graded retrospectively. RESULTS: Forty-five patients with 71 lesions were treated with CPAP-DIBH SBRT. Indications for CPAP-DIBH were prior radiation (35/71, 65%), lower lobe location (34/71, 48%), multiple lesions (26/71, 36.6%) and proximity to mediastinal OAR (7/71, 10%). Patient characteristics were: F:M 43%: 57%; mean gross tumor volume 4.5cm3 (SD 7.9), mean planning target volume 20cm3 (SD 27), primary: metastatic lesions (7%:93%). Mean radiation dose was 52.5 Gray (SD3.5). Mean lung volume was 5292cm3 (SD 1106). Mean duration of CPAP-DIBH was 41.3s (IQR 31-46.8). LC at 2 years was 89.5% (95% CI 76-95.5). In patients with central lesions, the distance between the tumor and mediastinal OAR increased from 0.84cm (SD 0.65) with FB to 1.23cm (SD 0.8) with CPAP-DIBH (p=0.002). Most patients tolerated CPAP well and completed all treatments after starting therapy. Three patients did not receive treatment: 2 were unable to tolerate CPAP and 1 had syncope (pre-existing). Toxicity was grade 2 in 4/65 (6%) and grade 3 in 1/65 (1.5%). There was no grade 2 or higher esophageal or tracheal toxicities. CONCLUSION: CPAP-DIBH assisted lung SBRT was tolerated well and was associated with minimal toxicity and favorable LC. This technique may be considered when treating multiple lung lesions, lesions located in the lower lobes or adjacent to mediastinal OAR.

Initial estimates of continuous positive airway pressure (CPAP) on heart volume, position and motion in patients receiving chest radiation.

To evaluate effects of Continuous Positive Airway Pressure (CPAP) on cardiac position, volume, and motion in a cohort of patients receiving thoracic radiation therapy (RT). Patients underwent 3-dimensional (3D) and 4D-computerized tomography (CT) imaging with free-breathing (FB) and CPAP for RT planning. All scans were co-registered on the treatment planning system for contouring, identification of the center of heart volume and comparative measurements of cardiac displacement, volume and motion. Heart volume (HV) was created from 3D-CT contours. Range of heart motion was estimated by creating an internal heart volume (IHV) from 4D-CT contours. Magnitude of cardiac motion (cardiac excursion) was recorded as the difference in volume between IHV and HV. Wilcoxon signed rank test and Spearmen's rank correlation coefficient were used to assess differences between variables and correlations between lung volume and heart parameters. Results from 9 patient data sets were available for this report. Compared to FB, CPAP use was associated with caudal displacement of the HV (1 cm, p < 0.008) and IHV (1.1 cm, p < 0.008). CPAP use decreased HV 6% (p < 0.008) and IHV 13% (p < 0.008). Cardiac excursion was 49% (p < 0.01) less with CPAP than with FB. CPAP use increased mean lung volume by 30% (p < 0.008) which correlated with caudal displacement of the HV (r = 0.83, p < 0.008) and IHV (r = 0.98, p < 0.001). The use of CPAP reduced cardiac motion and volume although the reduction in volume was minimal. The increase in lung volume correlated with caudal displacement of the heart. These results suggest the mechanism for achieving dosimetric benefit was obtained by cardiac displacement and decreased lung and heart motion rather than reduction of HV. Further evaluation of CPAP as a novel technique to reduce heart exposure when offering RT is warranted.

Noninvasive celiac plexus radiosurgery in palliative treatment for patients with symptomatic pancreatic cancer.

Advanced pancreatic cancer is commonly associated with significant visceral pain, radiating in a belt-like distribution to the upper abdomen, referring to the lower back, and significantly affecting patients' quality of life (QoL). The pain is often poorly controlled by pharmacotherapy, or the doses necessary to control the pain produce substantial adverse effects. Other available pain management options include invasive celiac plexus block or neurolysis, palliative radiotherapy, and systemic chemotherapy, all with limited efficacy. In this case report, we present the first non-invasive celiac plexus radiosurgery performed in Europe in a patient with pancreatic cancer, demonstrating that significant pain relief can be achieved through a non-invasive procedure performed within 2 outpatient visits.

COVID-RO study: the radiation oncology practice at times of COVID-19 outbreak - international survey.

BACKGROUND: Radiation therapy (RT), an essential treatment of cancer, involves multiple hospital visits. We hypothesized that radiation departments would adjust their work patterns and RT protocols in response to the SARS-CoV-2 pandemic. MATERIALS AND METHODS: An electronic survey was sent during April 2020 to an international sample of radiation oncologists. The survey explored various aspects of departmental preparedness, and changes to their institutional RT protocols. RESULTS: A total of 68 radiation oncologists from 13 countries answered the survey. Healthcare systems were at least moderately affected in 76%. Most institutes appeared well prepared for the outbreak: regarding the availability of personal protective equipment, tests, and telemedicine/videoconference facilities. Screening for SARS-CoV-2 was applied in 59% of responders. Modification of RT protocols were minor in 66%, significant in 19% and no changes made in 15%. The extent to which protocols were modified correlated with overall healthcare disruption (p = 0.028). Normal fractionation was recommended to continue in 83% and 85% of head & neck, and cervical cancers vs. 64% of lung cancers (p = 0.001).In case the pandemic worsens, there was strong agreement to prioritize RT for aggressive cancers (80%), delay RT for slow-growing tumors (78%) and change to evidance-based hypofractionations protocols (79.4%). The option of delayed/omitted adjuvant RT (not site specific) was selected in 47%. CONCLUSION: This international survey concludes that, by making significant organizational adjustments and minor protocol modifications, RT may be safely continued during this pandemic. If the crisis worsens, there was strong agreement to continue the treatment of aggressive tumors and utilize evidence-based hypofractionated protocols.

Benefits of Continuous Positive Airway Pressure (CPAP) During Radiation Therapy: A Prospective Trial.

PURPOSE: This study aimed to study the impact of continuous positive airway pressure (CPAP) on chest anatomy and tumor motion in patients receiving radiation therapy. METHODS AND MATERIALS: Patients with primary or secondary lung tumors, left-sided breast cancer, or liver metastases referred for radiation therapy were trained to breathe with a CPAP device using a face mask to a maximal pressure of 15 cm H2O. Three- and 4-dimensional computed tomography simulation was performed twice for each patient: once with free breathing (FB) and again using CPAP. Volumetric and dosimetric parameters of treatment plans were compared. RESULTS: Forty-nine patients were enrolled, of whom 6 withdrew consent before simulation and 3 withdrew because of discomfort. Thus, a total of 40 patients were analyzed. Twenty-seven patients (67.5%) were treated with CPAP based on confirmation of the volumetric or dosimetric benefit of CPAP. Mean lung volume increased by 37% (P < .001). The mean augmentation was 1283 ± 1128 cm3 (CPAP vs FB; P = .0006) in patients with normal lung function tests and 719 ± 341 cm3 (P = .003) in patients with a restrictive pattern. Increased lung volume was independent of age, body mass index, sex, chronic obstructive pulmonary disease, smoking status, and heart disease. Tumor motion in the lung was decreased as reflected in a mean reduction of planning target volume by 19% (P < .001). The greatest reduction of tumor trajectory and planning target volume occurred in tumors in the lower lung, particularly in the range of up to 6 cm above the dome of the diaphragm. The mean lung dose was reduced by 15%, lung V20 by 20%, lung V5 by 11%, and heart V5 by 16% (P < .01). CONCLUSIONS: In this prospective trial, the use of CPAP was associated with significant volumetric and dosimetric benefits compared with FB. CPAP was safe, simple to implement, and well tolerated by most patients, and it should be studied further as a method to reduce the risk of lung and heart toxicity.

Palliative radiation therapy for symptomatic advance breast cancer.

In this study, we evaluated the effectiveness of palliative breast radiation therapy (RT), with single fraction RT compared with fractionated RT. Our study showed that both RT fractionation schemas provide palliation. Single fraction RT allowed for treatment with minimal interference with systemic therapy, whereas fractionated RT provided a more durable palliative response. Due to equivalent palliative response, at our institution we have increasingly been providing single fraction RT palliation during the COVID-19 pandemic.

Mortality Among Neutropenic Cancer Patients Within the United States: The Association With Hospital Volume.

PURPOSE: Neutropenia is a serious complication of chemotherapy in patients with solid tumors. The influence of hospital volume on outcomes in patients with neutropenia has been little investigated. We hypothesized that large-volume hospitals would have reduced mortality rates for neutropenic patients compared with small-volume institutions. METHODS: We used the Nationwide Inpatient Sample database of the Healthcare Cost and Utilization Project, for the years 2007-2011. All adult inpatient episodes with a diagnosis of both neutropenia and solid-tumor malignancy were included. Hospital volume was defined as the number of neutropenic cancer episodes per institution per year. Mortality was defined as death during admission. A multilevel mixed-effects logistic regression model was applied. RESULTS: Twenty thousand three hundred and ten hospitalizations were included in the study, from 1,869 different institutions. Median age was 62 years. The overall inpatient mortality was 2.3%, and was dependent on age (age 50-59 years-1.6% and age 80-89 years-5.3%). The median number of neutropenic inpatient episodes in each institution per year was 14 (range, 1-168). Mortality was 3.3%, 2.7%, 2.2%, 2.2%, and 1.2% for each quintile of hospital volume (from lowest to highest volume, P < .001). Likewise, the proportion discharged home was 85.7%, 90.3%, 91.5%, 92.7%, and 95.4% (P < .001). The association between hospital volume and mortality remained significant after adjustment for patient-level and hospital-level variables. DISCUSSION: Patients with neutropenia hospitalized in large-volume institutions have a substantially lower mortality compared with those hospitalized at low-volume institutions. Further study is required to validate our findings or overcome potential biases, understand mechanism, and investigate how smaller institutions can improve outcomes.

Image-guidance triggered adaptive replanning of radiation therapy for locally advanced lung cancer: an evaluation of cases requiring plan adaptation.

OBJECTIVES: Anatomic changes may occur during chemoradiation treatment for lung cancers, requiring adaptive replanning. Here we characterize these cases. METHODS: We retrospectively studied lung cancer cases that underwent resimulation and adaptive replanning during 1/2016-3/2019. We compared first and second CT-simulation regarding tumor location, timing of change, tumor volume, anatomical alteration and change in simulation technique. We also compared dosimetric parameters between the plans, recorded local control, and overall survival outcomes. RESULTS: Out of 281 patients, 58 underwent replanning (20.6%). Histology included small cell (22.4%) and non-small cell (77.6%). Stage III was in 91.4%. Mean radiation dose of 59.4 Gray (Gy) (range 50-66Gy).Tumor location was peribronchial in 53.5%. Timing of replanning was in the first, second and final third of the treatment course in 26%, 43% and 31% respectively. Changes in gross tumor volume were observed in 74%; mean gross tumor volume was 276.7cc vs 192.7 cc (first vs second simulation, p = 0.001). Anatomical changes were identified in 35.4% including pleural fluid accumulation, atelectasis or pneumothorax alteration. Change in simulation technique was performed in 25.9%, including breath-hold or continuous positive airway pressure.Changes in dosimetric parameters when the same technique was used: lung V20Gy 26% (standard deviation, SD 7.6) vs 25.3% (SD 6.6) (p = 0.36), mean lung dose 15.1 Gy (SD 3.7) vs 14.7Gy (SD 3.3) (p = 0.23), heart V40Gy 10.2% (SD13) vs 7.2% (SD 9.8) (p = 0.037). When simulation technique changed: lung V20Gy 30.8% (SD 8.2) vs 27.3% (SD 8) (p = 0.012), mean lung dose 17.3 Gy (SD 4.4) vs 15.3 Gy (SD 3.8) (p = 0.007), heart V40Gy 11.1% (SD 14.7) vs 6.5% (SD 6.7) (p = 0.014).2 year local control was 60.7% (95% confidence interval, 34.5-79.2%), and median overall survival was 19.7 months. CONCLUSION: Adaptive replanning of radiation was performed in a fifth of locally advanced lung cancer patients. In most cases tumor volume decreased, or atelectasis resolved, causing mediastinal shifts, which, if unidentified and left uncorrected, may have led to local failure and increased toxicity. The heart V40Gy was reduced significantly in all cases, but significant reduction in lung doses was evident only if simulation technique was altered. ADVANCES IN KNOWLEDGE: In locally advanced lung cancer image-guidance with cone beam CT can detect significant mediastinal shifts and gross tumor volume changes that raise the need for adaptive replanning. Image guidance-triggered adaptive replanning should be added to the armament of advanced radiation treatment planning in locally advanced lung cancer.

Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy. METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT. RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72). CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes. ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT.

Accelerated Hypofractionated Radiation Therapy for Elderly Frail Bladder Cancer Patients Unfit for Surgery or Chemotherapy.

PURPOSE/OBJECTIVES: The main purpose of this study was to report treatment outcomes of definitive image-guided accelerated hypofractionated radiation therapy for elderly patients with muscle-invasive bladder cancer unsuitable for surgery or trimodality therapy. MATERIALS AND METHODS: Patients with confirmed muscle-invasive or high-risk T1 transitional cell carcinoma of the bladder, stage T1-T4aN0M0, who underwent transurethral resection of bladder tumor were irradiated with 45 Gy in 15 fractions. Comorbidity was assessed by Charlson Comorbidity Index. Cystoscopy, cytology, and computerised tomography imaging were used to evaluate treatment outcomes. RESULTS: Seventeen patients with a median age of 87 (range, 81 to 95) years and age-adjusted Charlson Comorbidity Index ≥3 were included. Transurethral resection of bladder tumor was incomplete in 65%. Radiation technique evolved from 3-dimensional conformal radiotherapy (3D CRT, 47%) to volumetric modulated arc therapy (VMAT, 53%). Ninety-four percent completed radiotherapy, with a median time of 20 days. The median follow-up was 65.3 months. Complete local response at 3-month cystoscopy was 69%. Six patients developed a local recurrence (35%), and 2 patients developed distant metastases (11.7%). Overall survival at 1 year was 47% and 23% at 2 years. Cancer-specific survival at 1 and 2 years were 85% and 63%, respectively. Acute grade 3 gastrointestinal or genitourinary toxicities were 6% and 24%, respectively. No grade 4 toxicity was documented. Diarrhea of any grade occurred in 35% of patients treated with 3D CRT, but in none of the patients treated with VMAT (P=0.002). CONCLUSIONS: Accelerated hypofractionated radiotherapy alone provides good local control in elderly patients unfit for chemoradiotherapy. Contemporary radiation techniques such as VMAT were associated with reduced bowel toxicity compared with 3D CRT.

Neo-adjuvant Chemo-Radiation to 60 Gray Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer Patients: Evaluation of Trimodality Strategy.

BACKGROUND: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy). OBJECTIVES: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery. METHODS: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50-62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52-87%), LC was 84% (95%CI 65-93), and DFS 35% (95%CI 14-59). Grade 4-5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01). CONCLUSIONS: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Short- and Long-Term Survival in Metastatic Pancreatic Adenocarcinoma, 1993-2013.

Background: During the past 2 decades, numerous clinical trials have focused on improving outcomes in patients with metastatic pancreatic cancer (mPDAC). The efficacy of new treatments has been demonstrated among highly selected patients in randomized phase III trials; hence, it is not clear to what extent these advances are reflected within the broader mPDAC population. Materials and Methods: Survival statistics were extracted from the SEER database for patients diagnosed with mPDAC between 1993 and 2013. Survival was analyzed using the Kaplan-Meier method and proportional hazard models. Results: The study population consisted of 57,263 patients diagnosed with mPDAC between 1993 and 2013; 52% were male, with a median age of 69 years (range, 15-104). Superior prognosis correlated with younger age, being married, tumor located within the head of the pancreas, lower grade disease, and more recent year of diagnosis. Median overall survival (OS) remained stable at 2 months between 1993 and 2013. Improvements in OS were seen for younger patients (age <50 years) and those with a more recent year of diagnosis (2009-2013). The percentage of patients who died within 2 months of initial diagnosis decreased between 1993 and 2013 (from 63.5% to 50.6%; P<.0001). The percentage of patients surviving ≥12 months improved from 4.9% in 1993 to 12.7% in 2013 (P<.0001). Conclusions: In recent years a modest improvement in OS has been seen among younger patients with mPDAC. The percentage of patients living beyond 1 year has significantly increased over time; however, the percentage of those dying within 2 months remains substantial.

Reexpansion of atelectasis caused by use of continuous positive airway pressure (CPAP) before radiation therapy (RT).

INTRODUCTION: Although radiation therapy (RT) is an effective treatment for malignant atelectasis, its accurate delivery is challenging because of difficulty differentiating between tumor and atelectatic lung. Furthermore, reexpansion of lung during treatment repositions tumor and normal structures necessitating replanning to ensure treatment accuracy. Facilitating lung reexpansion before initiation of RT may improve RT treatment accuracy, spare normal tissue, and reduce obstructive symptoms. We report a case of reexpansion of right upper lobe (RUL) atelectasis caused by use of continuous positive airway pressure (CPAP) before RT. CASE REPORT: A 52-year-old woman presented with dyspnea and cough. Imaging studies showed an RUL mass with atelectasis. Bronchoscopy showed extrinsic compression of the RUL and middle lobe bronchi. Biopsy showed small cell lung cancer. Staging with positron emission tomography-computed tomography (CT) and contrast enhanced CT of brain showed no other disease. Following 4 cycles of platinum-based chemotherapy, CT imaging showed a decrease in tumor volume, but persistent RUL atelectasis. She agreed to participate in an institutional study to evaluate the use of CPAP to reduce respiratory motion and immobilize tumors during RT. During CPAP training, she complained of vertigo, headache, and weakness and refused simulation. The next day she reported less dyspnea and completed training and CT simulation without difficulty. CT simulation with CPAP showed reexpansion of the RUL. Lung volume increased from 2170 to 3767 mL (74 %). Gross tumor volume, clinical volume, and planning volume decreased 46%, 45%, and 38%, respectively. Mean lung dose and mean heart dose decreased 20% and 51%, respectively. CPAP was used daily for 1 hour before and during treatment. Cone beam CT scans showed that the RUL remained inflated throughout treatment. CONCLUSION: This is the first reported use of CPAP for reexpansion of atelectasis before RT planning and treatment. Reexpansion of atelectasis improved RT planning, decreased dose to uninvolved lung, and removed the need for replanning. Further study of CPAP as an initial intervention to improve RT delivery in patients with malignant atelectasis is warranted.

Mitochondrial induction as a potential radio-sensitizer in lung cancer cells - a short report.

INTRODUCTION: Lung cancer is the leading cause of cancer death. Radiation therapy plays a key role in its treatment. Ionizing radiation induces cell death through chromosomal aberrations, which trigger mitotic catastrophe and apoptosis. However, many lung cancer patients show resistance to radiation. Dichloroacetate (DCA) is a small molecule that can promote mitochondrial activation by increasing the influx of pyruvate. Here, we tested whether DCA may increase the sensitivity of non-small cell lung cancer (NSCLC) cells to radiation through this mechanism. METHODS: Two representative NSCLC cell lines (A549 and H1299) were tested for their sensitivity to radiation with and without pre-exposure to DCA. The treatment efficacy was evaluated using a clonogenic survival assay. An extracellular flux analyzer was used to assess the effect of DCA on cellular oxygen consumption as a surrogate marker for mitochondrial activity. RESULTS: We found that DCA increases the oxygen consumption rate in both A549 and H1299 cells by 60% (p = 0.0037) and 20% (p = 0.0039), respectively. Pre-exposure to DCA one hour before radiation increased the cytotoxic death rate 4-fold in A549 cells (55 to 13%, p = 0.004) and 2-fold in H1299 cells (35 to 17%, p = 0.28) respectively, compared to radiation alone. CONCLUSION: Mitochondrial induction by DCA may serve as a radio-sensitizer in non-small cell lung cancer.

Transperineal implantation of gold fiducial markers (gold seeds) for prostate image-guided radiation therapy: a feasible technique associated with a low risk of complications.

INTRODUCTION: The purpose is to describe the method, safety and efficacy of transperineal gold seed placement for image-guided radiation therapy. METHODS: An ethics committee approved database was used to review records of consecutive patients from October 2008 through December 2013, who underwent transperineal implantation of three gold markers into the prostate using staged local anaesthesia and transrectal ultrasound. Seeds were counted on radiographs from CT simulation, first treatment and last treatment. Retention and use of at least three markers for kV/kV matching was considered a successful implant. A visual analogue scale (VAS) pain assessment was performed. SAS was used for data analysis. RESULTS: Fiducial marker placement was successful for kV/kV matching in 556/581 patients (95.7%). The procedure was aborted due to pain in two patients. Additional sedation during the procedure was required in two patients. Complications include urinary infections (2 patients, <0.5%) and transient haematuria (2 patients, <0.5%). There were no recorded calls requesting additional pain medication or delays in radiation due to complications. The number of seeds identified at simulation: 4 (2 patients), 3 (554 patients), 2 (21 patients), 1 (1 patient), 0 (1 patient). One patient with three seeds and two patients with <2 seeds had cone beam CT instead of kV/kV imaging for image guidance. No seeds were lost after simulation. The mean visual analogue pain score associated with transperineal gold seed insertion met patients' expectations (respectively 4.1 vs. 4.4 P = 0.19). CONCLUSION: Outpatient transperineal insertion of fiducials avoids the rectum, is effective, convenient, well tolerated and has few side effects.