Quality of life improvement in patients with bone metastases undergoing palliative radiotherapy.

Background: The aim of the study was to analyze the impact of palliative radiotherapy on quality of life (QoL) in patients with symptomatic bone metastases. Materials and methods: We present the results from a prospective multicentric study including 128 patients who provided pre- and post-radiotherapy (one month after treatment) brief pain inventory (BPI) assessments. Worst pain was recorded using the BPI (range: 0-10). Pain response was described according to the International Bone Metastases Consensus on palliative radiation. Regarding QoL, for each pre- and post-radiation BPI-questionnaire, scores from the interference domains were summed and averaged to obtain an overall interference score. Results: There was a significant correlation between radiation treatment response and improvement in all functional interference domains except sleeping. Patients > 75 years old presented a significantly higher improvement in general activity, mood and relationships with others compared to patients ≤ 75 years old. Patients presenting a baseline pain score ≥ 8 showed a higher improvement in the general activity item (p = 0.049). There was no statistically significant association between pretreatment ECOG, chemotherapy, primary tumor location and radiation schedule with any of the functional interference items. Conclusions: Patients who report pain relief after palliative radiotherapy also present a better quality of life including physical and psychosocial aspects.

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

BACKGROUND: The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined. AIM: To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS: Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014. RESULTS: 47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. "not reached" (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS. CONCLUSIONS: Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.

Late toxicity for prostate cancer patients treated with hypofractionated helical tomotherapy.

AIM: The purpose of this study is to evaluate the long term tolerability of hypofractionated helical tomotherapy (HT) in localized prostate cancer patients. BACKGROUND: Previous hypofractionated schedules with conventional RT were associated with excessive toxicity, likely due to inadequate sophistication of treatment delivery. There are few data about late toxicity after HT. MATERIALS AND METHODS: We evaluated 38 patients with primary adenocarcinoma of the prostate. There were 9 (24%), 15 (39%), and 14 (37%) patients with high, intermediate, and low risk, respectively. Patients were treated with hypofractionated HT from May 2008 to February 2011. Hypofractionation regimens included: 68.04 Gy at 2.52 Gy/fraction (N = 25; 66%), 70 Gy at 2.5 Gy/fraction (N = 4; 11%) and 70.2 Gy at 2.6 Gy/fraction (N = 9; 23%). Late genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. RESULTS: Median age at diagnosis was 70 years (range 49-80) and median follow-up, 5.8 years. Late grade 1, 2 and 3 GI toxicity were 13%, 24%, and 2.6%, respectively. Late grade 1, 2, 3 GU toxicity were 29%, 21%, and 8%, respectively. Sexual toxicity was evaluated in 19 patients to be grade 1, 2 in 11% and grade 3 in 16%. Multivariate analysis showed that patients with higher values of rectum V50 associated with late GI toxicity (P = 0.025). Patients with PSA ≤8 (P = 0.048) or comorbidities (P = 0.013) at diagnosis were associated with higher late GU toxicity. Additionally, PSA ≤8 also associated with moderate (grade ≥2) late GU toxicity in the multivariate analysis (P = 0.028). CONCLUSIONS: Hypofractionated HT can be delivered safely with limited rates of moderate and severe late toxicity. The proportion of the rectum that receives a moderate and high dose, having comorbidities, and PSA at diagnosis seem to associate with long term toxicity.

Robotic radiosurgery for the treatment of liver metastases.

AIM: This study evaluates the toxicity and outcome in patients treated with robotic radiosurgery for liver metastases. BACKGROUND: Modern technologies allow the delivery of high doses to the liver metastases while lowering the dose to the neighboring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known yet. METHODS AND MATERIALS: A total of 9 patients with 17 liver metastases have been treated with robotic stereotactic body radiotherapy SBRT from March 2011 to December 2014. Local response to SBRT was graded by the Response Evaluation Criteria in Solid Tumors criteria to describe change in treated tumor lesion. Adverse events after SBRT were graded on a 1-5 scale according to the National Cancer Institute common terminology criteria for adverse events v4.0. RESULTS: Patients received either three (78%) or five (22%) fractions. Patients were treated with a mean fraction dose of 14 Gy with a range from 9 to 20 Gy. The median total radiation dose provided to patients was 45 Gy with a range of 45-60 Gy. Four out of the 17 (23.5%) treated lesions had a complete response, 9 (53%) partial response and 3 (17.6%) stable disease. With a median follow-up of 15.2 months after SBRT treatment, local control and overall survival rated were 89% and 66%, respectively. No patient experienced grade ≥3 toxicity. The most common toxicity reported was asthenia. Only two patients had nausea and diarrhea, 10 and 14 days after SBRT, respectively. CONCLUSIONS: Robotic radiosurgery is a safe and effective local treatment option for secondary liver tumors. Further prospective studies are ongoing to determine long-term response and survival after robotic-SBRT for liver metastases.

Incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: multicenter prospective observational study.

BACKGROUND: Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. Pain flare, a transient worsening of the bone pain after RT, has been described in previous reports with different incidence rates. The aim of the study was to prospectively evaluate the incidence of pain flare following RT for painful bone metastases and evaluate its effects on pain control and functionality of the patients. METHODS: Between June 2010 and June 2014, 204 patients were enrolled in this study and 135 patients with complete data were evaluable. Pain flare was defined as a 2- point increase in worst pain score as compared with baseline with no decrease in analgesic intake or a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score. All pain medications and worst pain scores were collected before, daily during, and for 10 days after RT. The Brief Pain Inventory (BPI) was filled out on the pretreatment and at the 4 weeks follow-up visit. RESULTS: There were 90 men (66.7%) and 45 women (33.3%). Mean age was 66 years (SD 9.8). The most common primary cancer site was lung in 42 patients (31.1%), followed by prostate in 27 patients (20.0%). Forty-two patients (31.1%) patients received a single fraction of 8 Gy and 83 (61.5%) received 20 Gy in five fractions. The overall pain flare incidence across all centers was 51/135 (37.7%). The majority of pain flares occurred on days 1-5 (88.2%). The mean duration of the pain flare was 3 days (SD: 3). There were no significant relationships between the occurrence of pain flare and collected variables. All BPI items measured four weeks after end of RT showed significant improvement as compared with pretreatment scores (p < 0.001). No significant differences in BPI time trends were found between patients with and without flare pain. CONCLUSION: Pain flare is a common event, occurring in nearly 40% of the patients that receive palliative RT for symptomatic bone metastases. This phenomenon is not a predictor for pain response.

Rare breast tumors: Review of the literature.

Breast cancer tumors have different morphological phenotypes and specific histopathological types with particular prognostic and clinical characteristics. The treatment of rare malignant lesions is frequently controversial due to the absence of trials to determine the optimal managements. This review describes the spectrum of rare breast tumors indicating the clinical, epidemiological and treatment characteristics.

Saving lives, saving earth: hypofractionation and carbon footprint.

PURPOSE: The healthcare system contributes approximately 5% of global greenhouse gas emissions, yet the environmental impact of radiotherapy treatments remains inadequately assessed. MATERIAL AND METHODS: We selected all breast cancer patients (1959 patients) treated with adjuvant radiotherapy between 2015 and 2023 in one institution. We analyzed the CO2 emissions associated with travel. We also selected 60 patients randomly to analyze treatment-associated carbon emissions. We compared three different fractionation schemes: normofractionation (25-30 fractions, fx), hypofractionation (15-18fx), and ultra-hypofractionation (5-6fx). RESULTS: Our study revealed a significant reduction in carbon emissions within the 5-fractions group compared to the 15-fractions group (26.69kg vs 57.13kg, p < 0.001), saving approximately the CO2 emissions associated with the electricity consumption of an average Spanish household for 12 days, or the emissions of a passenger flying from Madrid to Barcelona. CONCLUSION: Most of the carbon footprint of radiotherapy is due to travel. Hypofractionation could be an appropriate solution to protect the environment.

Reirradiation salvage radiotherapy for recurrent prostate cancer after primary low-dose brachytherapy.

PURPOSE: Local recurrence of prostate cancer after low-dose rate brachytherapy is a clinical problem with limited salvage treatment options. This prospective study evaluated the tolerability and outcome of salvage external beam radiation therapy (S-EBRT) for locally recurrent prostate cancer after primary low-dose rate prostate brachytherapy (LDR-BT). MATERIALS AND METHODS: Between October 2012 and 2022, 18 patients with biopsy-proven locally recurrent prostate cancer after primary LDR-BT and received S-EBRT. We evaluated biochemical failure (BF), overall survival (OS) and acute/late gastrointestinal and urinary toxicities (CTCAE v5.0 or CTCAE v4, only before 2017). RESULTS: Median follow-up was 32 months (range, 5-124). The median age was at S-EBRT 68 years (range 59-79). 34% (6/18) were low risk, 44% (8/18) intermediate risk, 5% (1/18) high risk, and 17% (3/18) not specified. All patients were treated with IMRT/VMAT and received 60 Gy (2.5 Gy/fraction) to the prostate and 40% (7/18) 55.2 Gy (2,3 Gy/fx) to the seminal vesicles. 56% received ADT The 3-year OS and biochemical relapse-free survival after S-EBRT were 100% and 89%, respectively, with a median PSA nadir 0,035 ng/mL (0,01-0,34). Acute cystitis was present in 72% (13/18) of patients (27% of Grade > 2). Urethritis was present in 78% (14/18) patients (16% of cases Grade > 3), and acute rectitis occurred in 22% (4/18) of patients (no cases Grade > 3). CONCLUSIONS: Our data suggest that the treatment of locally recurrent prostate cancer with S-EBRT could provide adequate disease control safely and be used as an additional treatment in the natural history of prostate cancer patients. However, the results are still early and the sample is small; larger studies with longer follow-up would be mandatory.

Radiogenomics in lung cancer: Where are we?

Huge technological and biomedical advances have improved the survival and quality of life of lung cancer patients treated with radiotherapy. However, during treatment planning, a probability that the patient will experience adverse effects is assumed. Radiotoxicity is a complex entity that is largely dose-dependent but also has important intrinsic factors. One of the most studied is the genetic variants that may be associated with susceptibility to the development of adverse effects of radiotherapy. This review aims to present the current status of radiogenomics in lung cancer, integrating results obtained in association studies of SNPs (single nucleotide polymorphisms) related to radiotherapy toxicities. We conclude that despite numerous publications in this field, methodologies and endpoints vary greatly, making comparisons between studies difficult. Analyzing SNPs from the candidate gene approach, together with the study in cohorts limited by the sample size, has complicated the possibility of having validated results. All this delays the incorporation of genetic biomarkers in predictive models for clinical application. Thus, from all analysed SNPs, only 12 have great potential as esophagitis genetic risk factors and deserve further exploration. This review highlights the efforts that have been made to date in the radiogenomic study of radiotoxicity in lung cancer.

Haematological and renal toxicity of radiation therapy in neuroblastoma paediatric patients.

PURPOSE: The objective of this study was to evaluate the renal and hematologic toxicity in paediatric patients with adrenal high-risk neuroblastoma who have received radiation therapy (RT) as part of radical treatment. MATERIAL AND METHODS: Pediatric patients diagnosed with high-risk adrenal neuroblastoma who received RT as part of the definitive treatment between January 2004 and May 2020 in a single institution were selected. Complete blood counts (CBC) and creatinine clearance (CrCl) pre-RT and post-RT were compared through the Wilcoxon signed-rank test and correlated with survival analysis by Cox regression. RESULTS: Forty-two children with a median age of 3 years at diagnosis and 2.8 years of follow-up were selected. A significant and acute decrease in lymphocytes was found (p = 0.002) 1 month from RT. Patients with a drop higher than 50% of the previous value experimented a significant reduction in overall survival (55 vs 10%; p = 0.031). At the end of the follow-up, a significant increase in all blood counts was observed. With respect to renal function, an acute and significant decrease in CrCl was observed tin patients younger than 4 years who received RT (p = 0.013). However, it was not clinically relevant. CONCLUSION: Our data suggest that acute lymphopenia occurs after RT and could be associated with a poorer prognosis. Other blood counts are reduced after RT and all of them are in physiological range at the end of follow-up. Our cohort presented excellent renal outcomes without any case of chronic renal dysfunction.

New perspectives in radiation oncology: Young radiation oncologist point of view and challenges.

AIM: To assess the role of the young radiation oncologist in the context of important recent advancements in the field of radiation oncology, and to explore new perspectives and competencies of the young radiation oncologist. BACKGROUND: Radiation oncology is a field that has rapidly advanced over the last century. It holds a rich tradition of clinical care and evidence-based practice, and more recently has advanced with revolutionary innovations in technology and computer science, as well as pharmacology and molecular biology. MATERIALS AND METHODS: Several young radiation oncologists from different countries evaluated the current status and future directions of radiation oncology. RESULTS: For young radiation oncologists, it is important to reflect on the current practice and future directions of the specialty as it relates to the role of the radiation oncologist in the comprehensive management of cancer patients. Radiation oncologists are responsible for the radiation treatment provided to patients and its subsequent impact on patients' quality of life. Young radiation oncologists must proactively master new clinical, biological and technical information, as well as lead radiation oncology teams consisting of physicists, dosimetrists, nurses and technicians. CONCLUSIONS: The role of the young radiation oncologist in the field of oncology should be proactive in developing new competencies. Above all, it is important to remember that we are dealing with the family members and loved ones of many individuals during the most difficult part of their lives.

Primary squamous cell carcinoma of the breast: A rare case report.

BACKGROUND: Squamous cells are normally not found inside the breast. Therefore, a primary squamous cell carcinoma of the breast is an exceptional phenomenon and the management of this type of disease is still debated. AIM: Clinical outcome assessment of a patient with squamous cell carcinoma of the breast. MATERIALS AND METHODS: We report a case of primary squamous cell carcinoma of the breast (T1cN0M0) in a 51-years-old woman who underwent breast conserving surgery plus adjuvant chemotherapy and radiation therapy (RT). RESULTS: With a follow up of 43 months, the patient is alive with no evidence of local or distant recurrence. The patient had Grade 2 acute skin toxicity. No late skin or respiratory toxicity was observed. CONCLUSIONS: Pure primary squamous cell carcinoma of the breast is a rare and aggressive disease, often treatment-refractory. Our case shows that the addition of RT after breast conserving surgery, allows to achieve a high local control without adding severe toxicity. A multidisciplinary approach seems to be the optimal management for early stages in this rare disease.

Prospective multicentre analysis of the therapeutic approach and prognostic factors determining overall survival in elderly patients with non-small-cell lung carcinoma treated with curative intent.

Objective: To analyse patterns of treatment with curative intent commonly used in elderly patients with locally advanced non-small-cell lung carcinoma (NSCLC) and predictive factors of overall survival in routine clinical practice. Methods: This multicentre prospective study included consecutive patients aged ≥65 years old diagnosed with NSCLC between February 2014 and January 2018. Inclusion criteria: age ≥65 years, stage IIIA/IIIB NSCLC. Treatment decisions were taken by a multidisciplinary committee. Kaplan-Meier curves and log-rank test were used to identify which clinical/treatment-associated variables, or pre-treatment quality of life (QOL) considering EORTC QLQ-C30 (and LC13 module) were predictive of overall survival. Results: A total of 139 patients were recruited. Median follow-up was 9.9 months (1.18-57.36 months) with a median survival of 14 months (range 11-17 months). In the group>75-year-old patients, the committee recommended chemotherapy and sequential radiotherapy (55.6%) or radiotherapy alone (22.2%), rather than surgery (3.7%) or concomitant radiochemotherapy (16.5%). However, in 65- to 75-year-old patients, surgery and concomitant radiochemotherapy were recommended in half of cases (p=0.003). Regarding multivariate analysis, the risk of death was higher in patients with pre-existing heart disease (p=0.002), low score for physical functioning (p=0.0001), symptoms of dysphagia (p=0,01), chest pain (p=0.001), and those not undergoing surgical treatment (p=0.024). Conclusions: Patients >75 years received more conservative treatments. Surgery improved survival and should be carefully considered, regardless of patient age. Comorbidities and poor baseline QOL are predictive of shorter survival. Advances in knowledge: Measuring these parameters before treatment may help us to define a population of frail patients with a poorer prognosis to facilitate decision making in clinical practice.

Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study.

PURPOSE: Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS: This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS: Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION: Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.

Prognostic value of the TGFß1 rs4803455 single nucleotide polymorphism in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein ß1 (HSPB1) and transforming growth factor ß1 (TGFß1) and survival have been investigated. METHODS: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFß1 gene and 5 of HSPB1 gene) variables were analyzed. RESULTS: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFß1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. CONCLUSIONS: Genetic analysis showed the CA genotype of TGFß1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.

Optimizing lung cancer radiation treatment worldwide in COVID-19 outbreak.

COVID-19 has spread around the planet, sending billions of people into lockdown as health services struggle to cope. Meanwhile in Asia, where the disease began, the spread continues, in China it seems for now to have passed its peak. Italy, Spain, France, UK, and the US have been the countries more affected in terms of deaths. The coronavirus is more dangerous to the elderly and those with certain pre-existing medical conditions which is precisely the profile of lung cancer patients. Essential cancer services should be delivered but all steps should be taken to protect patients and the health workforce from infection with COVID-19. This presents a major challenge to radiotherapy (RT) departments worldwide. An international panel with expertise in the management of lung cancer in high-volume comprehensive centres has come together to share its experience on COVID-19 preparedness to deliver optimal care in such exceptional circumstances. A comprehensive systematic review of the literature through a PubMed search was undertaken. Twelve recommendations including, among others, the consideration of shorter courses, delays, and the omission of RT for lung cancer are proposed by the panel. In summary, we recommend the screening of every single person accessing the treatment room, the consideration of hypofractionation and to delay postoperative RT for non-small cell lung cancer, to avoid twice-daily treatments and delay or deliver prophylactic cranial irradiation during radio(chemo)therapy for limited-stage small cell lung cancer, review image guided RT images for suspicious image findings, and the use of single-fraction RT for the palliative treatment of stage IV lung cancer patients. Given that lung cancer is one of the most common and severe pathologies in radiation oncology departments, the following recommendations require particularly urgent consideration. The decision-making paths strongly depend on locally available resources, and a tailored approach should be used to attend lung cancer patients during this pandemic.

Overexpression of Canonical Prefoldin Associates with the Risk of Mortality and Metastasis in Non-Small Cell Lung Cancer.

Canonical prefoldin is a protein cochaperone composed of six different subunits (PFDN1 to 6). PFDN1 overexpression promotes epithelial-mesenchymal transition (EMT) and increases the growth of xenograft lung cancer (LC) cell lines. We investigated whether this putative involvement of canonical PFDN in LC translates into the clinic. First, the mRNA expression of 518 non-small cell LC (NSCLC) cases from The Cancer Genome Atlas (TCGA) database was evaluated. Patients with PFDN1 overexpression had lower overall survival (OS; 45 vs. 86 months; p = 0.034). We then assessed the impact of PFDN expression on outcome in 58 NSCLC patients with available tumor tissue samples. PFDN1, 3, and 5 overexpression were found in 38% (n = 22), 53% (n = 31), and 41% (n = 24) of tumor samples. PFDN1, 3, and 5 overexpression were significantly associated with lower OS, lower disease-free survival (DFS), and lower distant metastasis-free survival (DMFS) for PFDN1 and 3 with a trend for PFDN5. In multivariate analysis, PFDN5 retained significance for OS (hazard ratio (HR) 2.56; p = 0.007) and PFDN1 for DFS (HR 2.53; p = 0.010) and marginally for DMFS (HR 2.32; p = 0.053). Our results indicate that protein response markers, such as PFDN1, 3, and 5, may complement mRNA signatures and be useful for determining the most appropriate therapy for NSCLC patients.

The single nucleotide variant rs2868371 associates with the risk of mortality in non-small cell lung cancer patients: A multicenter prospective validation.

BACKGROUND AND PURPOSE: Definitive radiation therapy (RT) with or without chemotherapy has become the standard treatment for non-metastatic unresectable non-small cell lung cancer (NSCLC). However, treatment outcomes can differ substantially and patients' genetic background could play a crucial role. Potential associations between single-nucleotide polymorphisms (SNP) in Heat shock protein beta-1 (HSPB1) and survival have been reported in prior single-institution retrospective reports. MATERIALS AND METHODS: The current assay aims to validate such connection in a prospective multicenter study in a European cohort including 181 NSCLC patients. Median follow-up time for all patients was 13 months (range, 3-57 months). RESULTS: The results obtained show an association between the rs2868371 GG genotype and better overall survival (HR: 0.35; 95%CI: 0.13-0.96; p = 0.042) in multivariate analysis. Two-year overall survival rate was 72% for patients carrying the rs2868371 GG genotype versus 36% for those patients harboring the rs2868371 CC/CG genotypes (p = 0.013). Additionally, the rs2868371 GG genotype was found to be associated with better disease-free survival in the multivariate analysis (HR: 0.36; 95%CI: 0.13-0.99; p = 0.048). In silico analysis of the potential functional SNP suggested significant difference in the affinity of the Glucocorticoid Receptor binding site between alternative allelic variants, confirmed by chromatin immunoprecipitation analysis displaying stronger affinity for the risk allele (C). Furthermore, our findings indicate that the rs2868371 influences (mRNA) HSPB1 expression, offering insight into the regulation of HSPB1 transcription. CONCLUSION: The functional HSPB1 rs2868371 promoter variant may affect lung cancer survival by regulation of HSPB1 expression levels through glucocorticoid receptor interaction.

Association of single nucleotide polymorphisms at HSPB1 rs7459185 and TGFB1 rs11466353 with radiation esophagitis in lung cancer.

BACKGROUND AND PURPOSE: Radiochemotherapy (RCT) success in lung cancer (LC) can be limited due to the onset of adverse effects in the adjacent normal tissue such as radiation-induced esophageal toxicity (RIET). Therefore, specific biomarkers to customize the RCT dose administration and esophageal toxicity prediction are necessary to improve treatment effectiveness. MATERIALS AND METHODS: 247 LC patients prospectively recruited between 2012 and 2016 from 3 institutions were genotyped for 7 SNPs along TGFB1 and HSPB1 genes seeking an association with RIET risk development. Kaplan-Meier cumulative probability and Cox proportional hazards analyses were used to evaluate the effect of TGFB1 and HSPB1 genotypes on such risk. RESULTS: Multivariate analyses showed that patients carrying the HSPB1 rs7459185 CC genotype were associated with a significantly higher risk of acute grade 3 RIET than those carrying the GG/GC genotypes (HR = 17.73; 95% CI = 2.896-108.49; p = 0.002). LC patients who received higher (>median) volume of esophagus exposed to 30 Gy and harboring the rs7459185 GG/GC genotypes showed a significantly lower RIET incidence (p < 0.001). Additionally, LC patients carrying the TGFB1 rs11466353 GG genotype were found to be associated with a lower risk of late grade 2 RIET compared with those with the TT/TG genotypes (HR = 0.29; 95% CI = 0.103-0.830; p = 0.021). Patients receiving a high (>60 Gy) radiation dose who presented the rs11466353 GG genotype had a significantly lower RIET incidence (p = 0.025). CONCLUSION: The presence of different rs7459185/rs11466353 genotypes in LC patients associated with RIET risk and may be useful biomarkers along with other risk factors for guiding therapy intensity in an individualized therapy.