Does adaptive radiotherapy for head and neck cancer favorably impact dosimetric, clinical, and toxicity outcomes?: A review.

PURPOSE: The current review aims to summarize the international experience of the impact of adaptive radiotherapy on dosimetry and clinical and toxicity outcomes. Additionally, it might trigger Radiation Oncologists to use ART and evaluate whether ART improves target volume coverage and/or normal tissue sparing and, consequently, therapeutic results. MATERIALS AND METHODS: We conducted an electronic literature search of PubMed/MEDLINE and ScienceDirect from January 2007 to January 2023. The search adhered to the PRISMA guidelines and employed keywords such as ART, HNC, parotid gland, and target volume. Furthermore, we examined the reference lists for studies pertinent to the present review. This study included both retrospective and prospective studies that were considered for inclusion. CONCLUSION: ART replanning appears to be a sustainable strategy to minimize toxicity by improving normal tissue sparing. Furthermore, it can enhance target volume coverage by correctly determining the specific dose to be delivered to the tumor. In conclusion, this review confirmed that ART benefits dosimetric, clinical/therapeutic, and toxicity outcomes.

Vaginal dilator use to promote sexual wellbeing after radiotherapy in gynecological cancer survivors.

ABSTRACT: This study investigated the efficacy of a vaginal dilator (VD) for the treatment of radiation-induced vaginal stenosis (VS) and the effect of a VD on sexual quality of life.Fifty three patients with endometrial or cervical cancers participated in this prospective observational study. All participants were treated with radical or adjuvant external beam radiotherapy and/or brachytherapy. They were routinely examined 4 times after radiotherapy (RT) and were also asked to complete a validated sexual function-vaginal changes questionnaire. SPSS version 20 and Minitab version 16 were used for the statistical analysis. The statistical significance was set at P < .05.The VS grading score decreased and the comfortably insertable VD size gradually increased throughout a year of VD use; all patients with initial grade 3 showed a VS of grade 2 after 12 months of VD use and 65.8% of the patients with initial grade 2 demonstrated a final VS of grade 1, while 77.8% of the participants who started with the first size of VD reached the third size after 12 months. Starting VD therapy ≤3 months after the end of RT was associated with a significant decrease in VS. A total of 60.9% of participants reported that they did not feel their vaginas were too small during intercourse after 12 months of dilation, whereas only 11.5% gave the same answer before starting dilation. Furthermore, 47.17% rated their satisfaction with their sexual life 5 out of 7 and only 3.77% gave a score of 3 after 12 months of dilation.Endometrial and cervical cancer survivors are encouraged to use VD to treat VS and for sexual rehabilitation after RT. This study recommends starting vaginal dilation no more than 3 months after treatment at least 2 to 3 times a week for 10 to 15 minutes over 12 months. However, larger, well-designed randomized clinical trials should be conducted to develop specific guidelines for VD use and efficacy in VS and sexual sexual quality of life after RT.

Is Locally Advanced Head-Neck Cancer One More Candidate for Accelerated Hypofractionation?

BACKGROUND/AIM: Hypofractionated accelerated radiotherapy (HypoAR) is widely applied for the treatment of early laryngeal cancer. Its role in locally advanced head-neck cancer (LA-HNC) is unexplored. PATIENTS AND METHODS: We present results of a prospective trial on 124 patients with LA-HNC, treated with radio-chemotherapy with three different HypoAR fractionations (3.5 Gy/day × 14-15 fractions, 2.7 Gy/day × 20-21 fractions, and 2.5 Gy/day × 21-22 fractions). RESULTS: Protraction of the overall treatment time due to oropharyngeal mucositis was enforced in 18/57 laryngeal, 6/19 nasopharyngeal, and 15/48 cancer patients with other tumors. Regarding late toxicities, laryngeal edema grade 3 was noted in 5/57 patients with laryngeal cancer, while severe dysphagia was noted in 4/124 and tracheoesophageal fistula formation in 1/124 patients. The complete response rates obtained were 73%, 84%, and 67% in patients with laryngeal, nasopharyngeal, and other tumors, respectively. The 3-year locoregional progression-free survival was 58%, 73%, and 55%, respectively. CONCLUSION: HypoAR chemoradiotherapy is feasible, with acceptable early and late radiotherapy toxicities, response rates and LPFS.

Modern radiopharmaceuticals for lung cancer imaging with positron emission tomography/computed tomography scan: A systematic review.

INTRODUCTION: In this study, we evaluated the use and the contribution of radiopharmaceuticals to the field of lung neoplasms imaging using positron emission tomography/computed tomography. METHODS: We conducted review of the current literature at PubMed/MEDLINE until February 2020. The search language was English. RESULTS: The most widely used radiopharmaceuticals are the following:Experimental/pre-clinical approaches: (18)F-Misonidazole (18F-MISO) under clinical development, D(18)F-Fluoro-Methyl-Tyrosine (18F-FMT), 18F-FAMT (L-[3-18F] (18)F-Fluorothymidine (18F-FLT)), (18)F-Fluoro-Azomycin-Arabinoside (18F-FAZA), (68)Ga-Neomannosylated-Human-Serum-Albumin (68Ga-MSA) (23), (68)Ga-Tetraazacyclododecane (68Ga-DOTA) (as theranostic agent), (11)C-Methionine (11C-MET), 18F-FPDOPA, ανß3 integrin, 68Ga-RGD2, 64Cu-DOTA-RGD, 18F-Alfatide, Folate Radio tracers, and immuno-positron emission tomography radiopharmaceutical agents.Clinically approved procedures/radiopharmaceuticals agents: (18)F-Fluoro-Deoxy-Glucose (18F-FDG), (18)F-sodium fluoride (18F-NaF) (bone metastases), and (68)Ga-Tetraazacyclododecane (68Ga-DOTA). The quantitative determination and the change in radiopharmaceutical uptake parameters such as standard uptake value, metabolic tumor volume, total lesion glycolysis, FAZA tumor to muscle ratio, standard uptake value tumor to liver ratio, standard uptake value tumor to spleen ratio, standard uptake value maximum ratio, and the degree of hypoxia have prognostic and predictive (concerning the therapeutic outcome) value. They have been associated with the assessment of overall survival and disease free survival. With the positron emission tomography/computed tomography radiopharmaceuticals, the sensitivity and the specificity of the method have increased. CONCLUSION: In terms of lung cancer, positron emission tomography/computed tomography may have clinical application and utility (a) in personalizing treatment, (b) as a biomarker for the estimation of overall survival, disease free survival, and (c) apply a cost-effective patient approach because it reveals focuses of the disease, which are not found with the other imaging methods.

Acute Leriche Syndrome in Pancreatic Adenocarcinoma: A Case Report.

INTRODUCTION: Coexistance of pancreatic carcinoma and Leriche syndrome is an extremely rare pathological condition. Leriche syndrome is defined as occlusion of the distal aorta at the bifurcation into the common iliac arteries. CASE REPORT: We report the case of a 57-year old male patient with a locally advanced pancreatic tumor that during chemotherapy presented Leriche syndrome. Four months after the diagnosis and although the initial staging by MRI had only revealed a few atheromatic lesions of the abdominal aorta, the patient complained about claudication of the legs and hypoesthesia. Angiography with multi-detector computed tomography (MDCTA) was performed using aortography protocol and three-dimensional reconstruction of the images followed, demonstrating the relationship between pancreatic carcinoma and Leriche syndrome. CONCLUSION: Review of the literature revealed that acute abdominal thrombosis is rare in cancer patients. To our knowledge, complete occlusion of the aorta in a patient with pancreatic cancer has not been reported yet.

Differential Diagnosis of Behavioral Variant and Semantic Variant of Frontotemporal Dementia Using Visual Rating Scales.

BACKGROUND: Frontotemporal dementia (FTD) represents the second most frequent early onset of dementia in people younger than 65 years. The main syndromes encompassed by the term FTD are behavioral variant of Frontotemporal dementia (bvFTD), non-fluent variant primary progressive aphasia (nfvPPA) and semantic variant (SD). AIMS: To assess the bvFTD and SD, which represent the most common subtypes of FTD, using visual rating scales. METHODS: Brain MRI exams of 77 patients either with bvFTD (n=43) or SD (n=34) were evaluated. The rating scales used were: Global cortical atrophy (GCA), Fazekas Scale: periventricular (PV) and white matter (WM) changes, Koedam rating scale and visual scales regarding specific cortical regions: dorsofrontal (DF), orbitofrontal (OF), anterior cingulate (AC), basal ganglia (BG), anterior- temporal (AT), insula, lateral-temporal (LT), entorhinal (ERC), perirhinal (PRC), anterior fusiform( AF), anterior hippocampus (AHIP) and posterior hippocampus (PHIP). Both Left (L) and Right (R) hemispheres were evaluated. RESULTS: R-OF (p=0.059), L-OF (p<0.0005), L-AT (p=0.047) and L-AHIP (p=0.007) have a statistically significant effect on the variable occurrence of SD compared to bvFTD. The indicators with the highest value of the area under the curve (AUC) were R-AC (0.829), L-OF (0.808), L-AC (0.791) and L-AF (0.778). Highest sensitivity was achieved by R-OF (97%) and L-AF (75%). Highest specificity was achieved by L-OF (95%), L-AT (91%) followed by R-AC (84%). Best combination of sensitivity and specificity was achieved by L-AF (74%-79%), L-OF (56%-95%) and R-OF (97%-42%). Best combination of PPV and NPV was achieved by L-OF (90%-73%), LAT (83%-72%) and R-AC (77%-77%). CONCLUSION: Visual rating scales can be a practical diagnostic tool in the characterization of patterns of atrophy in FTLD and may be used as an alternative to highly technical methods of quantification.

Evaluation of the Irradiated Volume of the Heart and Cardiac Substructures After Left Breast Radiotherapy.

Backround/Aim: Adjuvant radiotherapy in patients with cancer of the left breast may lead to impaired cardiac function. The aim of our prospective study is to evaluate (i) doses to the irradiated volume of the heart and its substructures and (ii) determine whether their correlation with changes in strain echo measurements contribute to the prediction of subclinical heart morbidity. PATIENTS AND METHODS: Twenty-five patients were enrolled in our study. We retrospectively assessed the radiation doses to the whole heart, left anterior descending artery (LAD) and left ventricle (LV). RESULTS: The mean heart dose (MHD) was 152 cGy (SD=50.56 cGy) and the range was 74-279 cGy. The LAD was the most exposed structure, with a mean dose of 448.91 cGy (SD=490.53 cGy) and range of 120-2,057cGy. Finally, the mean LV dose was 149.12 cGy (SD=69.57) with a range of 63-317 cGy. CONCLUSION: The early results of our study showed low radiation exposure of the whole heart and left ventricle, and higher exposure of the LAD. The data that will emerge from the evaluation of strain echo parameters should show whether these associations might be useful in clinical practice for the prediction of early subclinical cardiac changes.

Benign Intracranial Lesions - Radiotherapy: An Overview of Treatment Options, Indications and Therapeutic Results.

BACKGROUND: Radiation Therapy (RT) is an established treatment option for benign intracranial lesions. The aim of this study is to display an update on the role of RT concerning the most frequent benign brain lesions and tumors. METHODS: Published articles about RT and meningiomas, Vestibular Schwannomas (VSs), Pituitary Adenomas (PAs), Arteriovenous Malformations (AVMs) and craniopharyngiomas were reviewed and extracted data were used. RESULTS: In meningiomas RT is applied as an adjuvant therapy, in case of patientrefusing surgery or in unresectable tumors. The available techniques are External Beam RT (EBRT) and stereotactic ones such as Stereotactic Radiosurgery (SRS), Fractionated Stereotactic RT (FSRT), Intensity Modulated RT (IMRT) and proton-beam therapy. The same indications are considered in PAs, in which SRS and FSRT achieve excellent tumor control rate (92-100%), acceptable hormone remission rates (>50%) and decreased Adverse Radiation Effects (AREs). Upon tumor growth or neurological deterioration, RT emerges as alone or adjuvant treatment against VSs, with SRS, FSRT, EBRT or protonbeam therapy presenting excellent tumor control growth (>90%), facial nerve (84-100%), trigeminal nerve (74-99%) and hearing (>50%) preservation. SRS poses an effective treatment modality of certain AVMs, demonstrating a 3-year obliteration rate of 80%. Lastly, a combination of microsurgery and RT presents equal local control and 5-year survival rate (>90%) but improved toxicity profile compared to total resection in case of craniopharyngiomas. CONCLUSION: RT comprises an effective treatment modality of benign brain and intracranial lesions. By minimizing its AREs with optimal use, RT projects as a potent tool against such diseases.

Evaluation of quality of life outcomes following palliative radiotherapy in bone metastases: A literature review.

PURPOSE: To assess the quality of life (QoL) following palliative radiotherapy (RT) in patients with painful bone metastases. METHODS: A literature search limited to English-written publications was carried out, through the Cochrane Central Register of Controlled Trials (November 2018), OvidSP and PubMedCentral (1940-November 2018) databases. Subject headings and keywords included "quality of life"(QoL), "bone metastases", "palliative therapy", "pain" and "radiotherapy". Original articles, literature reviews, trials and meta-analyses revealing alterations in QoL post-RT using ratified measuring tools were examined. Studies referring to other types of metastases (e.g. brain metastases), or to other types of palliative therapy (e.g. the use of bisphosphonates alone), or focusing only on pain, or even reporting QoL only before or only after the use of RT were excluded. RESULTS: Twenty four articles were selected from a total of 1360 articles. Seven trials proceeded to patients' randomization. The most commonly used tool to evaluate QoL was EORTC, followed by Brief Pain Inventory (BPI) and Edmonton Symptom Assessment System (ESAS) questionnaires. All studies showed improvement in symptoms and functional interference scores after RT. The QoL between responders (Rs) and non-responders (NRs) has been juxtaposed in 10 studies. Rs had a significant benefit in QoL in comparison with the NRs. DISCUSSION: Palliative radiotherapy in painful bone metastases improves Rs' QoL.

Perioperative inadvertent hypothermia among urology patients who underwent transurethral resection with either TURis or transurethral resection of the prostate method.

PURPOSE: The purpose of the study was to investigate the incidence of perioperative hypothermia in urology patients undergoing transurethral resection with either TURis or transurethral resection of the prostate method and to recognize the risk factors that were responsible for the occurrence of hypothermia intraoperatively in these patients. METHODS: It was a randomized prospective study. A total of 168 patients, according to American Society of Anesthesiologists physical status I-III, were scheduled for transurethral resection either with TURis or transurethral resection of the prostate method. We measured the core body temperature before (preoperative), during (perioperative) and after (postoperative) the surgery. Age, body mass index, American Society of Anesthesiologists score, duration of surgery, preoperative prostatic volume, and vital signs were also recorded. RESULTS: The prevalence of inadvertent hypothermia was 64.1% for the TURis group and 60% for the transurethral resection of the prostate group. Hypothermic patients in TURis group were significantly older (87.7 ± 1.7 vs 68 ± 6.7 years, p < 0.05) and had lower body mass index (26.9 ± 3.6 vs 29.2 ± 2.7, p < 0.05), while hypothermic patients in the transurethral resection of the prostate group were significantly older (86 ± 1.1 vs 70 ± 7.4 years, p < 0.05) and had notably higher duration of surgery (140.6 ± 28.9 vs 120.3 ± 14.3 min, p < 0.05) than normothermic patients. CONCLUSION: Perioperative inadvertent hypothermia among urology patients who underwent transurethral resection with both TURis and transurethral resection of the prostate method is of high incidence. We recommend monitoring of the temperature of core body of all these patients, especially those with advanced age and lower body mass index.

Clinical value of significance of Hypoxia Inducible Factor-1α, Glucose Transporter-1 and Carbonic Anhydrase IX in rectal cancer after preoperative chemoradiotherapy.

PURPOSE: The standard treatment of rectal cancer is surgery along with preoperative radiotherapy, administered alone or in combination with chemotherapy. Preoperative chemoradiotherapy (preCRT) is widely used as it allows better local control and the use of sphincter-saving surgery. Pathological response after preCRT has been shown to be a significant prognostic factor of rectal cancer recurrence and survival. In this review we will assess the value of Hypoxia Induced Factor 1α (HIF-1α), Carbonic Anhydrase IX (CA-9) and Glucose Transporter 1 (GLUT-1) genes as predictive markers of the course of local advanced rectal cancer in patients who underwent pre-CRT. METHODS: We searched studies, from Pubmed and in English language, obtained the information by using "HIF-1 alpha", "Carbonic Anhydrase IX (CA-9)", "Glucose Transporter 1 (GLUT-1)" and "rectal cancer" as key words. RESULTS: 27 relevant articles were retrieved in initial stage. After full-text review, 13 articles were selected for the final analysis. CONCLUSIONS: HIF-1α, GLUT-1 and CA-IX may be connected with tumor response to preCRT, however, there is still skepticism towards their clinical use as predictors of outcome. Therefore, there is a need to conduct larger and more extensive cohort studies in order to find whether these predictors can be used in practice.

Breast Radiotherapy and Early Adverse Cardiac Effects. The Role of Serum Biomarkers and Strain Echocardiography.

Breast cancer radiotherapy has a clear benefit for both long-term survival and local recurrence rate. However, there is still much concern about the early radiation-induced heart toxicity. This article aimed to clarify the impact of certain cardiac biomarkers and strain echocardiographic imaging on the detection of early cardiac dysfunction. Several studies that reported changes in either echocardiographic and/or serum levels measurements after breast radiotherapy were searched. Despite the established role of cardiac biomarkers to predict late cardiotoxicity after radiotherapy, data concerning early cardiac damage are still lacking. Furthermore, although strain echocardiography represents a specific tool for the detection of cardiac morbidity in certain diseases, much interest concerns its role in the prediction of early heart failure after radiotherapy. Identification of new tools for the detection of early cardiotoxicity after breast radiotherapy may minimize the side-effects of therapeutic modalities in the clinical setting.

Percutaneous computed tomography-guided localization of pulmonary nodules with hook wire prior to video-assisted thoracoscopic surgery.

PURPOSE: To evaluate the use of percutaneous computed tomography (CT)-guided localization of suspicious intrapulmonary nodules with hook wire prior to video-assisted thoracoscopic surgery (VATS). METHODS: From April 2010 to February 2011, 15 patients with suspicious subpleural pulmonary nodules underwent preoperative CT-guided hook wire localization of the lesions, prior to VATS. RESULTS: Histological analysis of the resected suspicious pulmonary nodules revealed malignancy in 12 cases, 2 cases with granulomas and 1 case with bronchiolitis obliterans organizing pneumonia (BOOP). Better results were achieved with the double-thorn hook wire. Conversion to thoracotomy was necessary in the patient with BOOP, due to limited hemorrhage at the site of the lesion. CONCLUSION: Preoperative CT-guided nodule localization using hook wire fixation is a useful and safe technique that helps in the precise localization of suspicious lesions, reduces the operation time, the postoperative complications, and the hospitalization.

Immunotherapy of Cancer: Developments and Reference Points, an Unorthodox Approach.

Oncology is currently a sector of medical science with accelerated progress due to rapid technological development, the advancement in molecular biology, and the invention of many innovative therapies. Immunotherapy partially accounts for this advance, since it is increasingly playing an important role in the treatment of cancer patients, bringing on a sense of hope and optimism through a series of clinical studies and cases with spectacular results. Immunotherapy, after the initial successes it experienced in the early 20th century, was forgotten after chemotherapy and radiotherapy prevailed and developed slowly in the background. Today, it is the new hope for cancer treatment, despite the unorthodox path it has followed. In this article, we study the course and key points of the discovery of immune-oncology from the oncologist's point of view. We also record the questions that have been posed about immunotherapy that sometimes lead to confusion or stalemate.

Systemic therapy of metastatic renal cell carcinoma: Review of the current literature.

INTRODUCTION:: Renal cell carcinoma represents a neoplasm with usually aggressive behavior. Due to its nature, it is often diagnosed in an advanced stage or when metastatic dissemination has been occurred. The aim of this review is to provide an overview of the current management of metastatic renal cell carcinoma and briefly discuss the potential new therapeutic strategies for this disease. METHODS:: Review of the literature was performed in PubMed/MEDLINE, Cochrane, and EMBASE and we included English articles up to February 2018. RESULTS:: Over the past years, many efforts have been made in the context of confronting metastatic disease and led to the introduction of targeted therapies. More available agent options, including various tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, can be served nowadays as the first-, second-, and third-line therapy in the metastatic setting of the disease providing better outcomes. DISCUSSION:: Moreover, regarding the recent advances in the field of cancer immunotherapy, the landscape of metastatic renal cell carcinoma management is being shaped toward novel immunotherapeutic interventions alone or in combination with other types of therapy.

A five split-field three dimensional conformal technique versus an anterior-posterior on in postoperative radiotherapy for gastric carcinoma: a multicenter comparative study using quality of life measurements as well as clinical and dosimetric parameters.

PURPOSE: Several adjuvant approaches are regarded as available options in the management of localized, resectable gastric cancer .The objective of our study was to evaluate multiple field and anteroposterior conformal technique. METHODS: Ninety-seven patients received three dimensional conformal (3DCRT) postoperative adjuvant radiation therapy for gastric carcinoma. Thirty-five patients received anteroposterior (AP/PA) fields (Group B), while 62 patients were irradiated with multifield technique (Group A). Their ages ranged between 29-85 years. The objective of the study was to evaluate the quality of life (QoL) for all patients after the completion of radiotherapy using the QLQ-C30 of the EORTC questionnaire (European Organization for Research and Treatment of Cancer) and to investigate any measurable differences between those two radiation techniques according to QUANTEC criteria and the radiotoxicity. RESULTS: In terms of QUANTEC criteria, the multifield technique was superior concerning the left kidney (p=0.025), right kidney (p<0.001), spinal cord (p<0.001) and planning target volume (PTV) coverage (p<0.001). According to EORTC/ RTOG toxicity criteria, the rate of diarrhea was higher in AP/ PA technique (p=0.028). In terms of QLQ-C30, the multifield technique was superior concerning appetite loss (p=0.022), diarrhea (p=0.046) and global QoL (p<0.001). CONCLUSION: On the basis of QLQ-C30 questionnaire, EORTC/ RTOG toxicity and dosimetric parameters, the present report has shown that the three dimensional multifield conformal radiotherapy is superior compared to AP-PA techniques.

Utilizing Yoga in Oncologic Patients Treated with Radiotherapy: Review.

PURPOSE: Several trials on noncancer population indicate that yoga is associated with meaningful clinical effects. This study evaluated the physical and psychosocial outcomes of yoga in oncologic patients treated with radiotherapy. METHODS: We focused on a research through Cochrane Register of Controlled Trials (CENTRAL), BioMed Central, and MEDLINE studies up to May 2017. RESULTS: Yoga was found to have a substantial benefit in cancer patients' distress, anxiety, and depression. It also demonstrated a moderate impact on fatigue and emotional function and a small and insignificant effect on functional well-being and sleep disturbances. As far as the effects on psychological outcomes are concerned, there was insufficient evidence. CONCLUSIONS: This systematic review of randomized controlled trials showed that yoga has strong beneficial effects on oncologic patients' quality of life. Results of the current review must be interpreted with caution due to the relative small sample sizes of most of the included studies, while a prospective randomized study stands in need for the confirmation of our results.

Estimating the agreement between the metabolic rate calculated from prediction equations and from a portable indirect calorimetry device: an effort to develop a new equation for predicting resting metabolic rate.

BACKGROUND: Many studies have been performed over time in order to determine the reliability of metabolic rate prediction equations. PURPOSE: To evaluate the agreement, in terms of bias, absolute bias and accuracy between metabolic rate prediction equations and measured metabolic rate using indirect calorimetry system (IC), investigating also the factors affecting this agreement. METHODS: The anthropometric features of 383 Caucasian participants of all Body Mass Index (BMI) classes were recorded and Resting Metabolic Rate (RMR) was measured by using the IC Fitmate portable device. The resulting values were compared with the predictive values of Harris & Benedict, Schofield, Owen, FAO-WHO-UNU, Mifflin and Harrington equations. RESULTS: A closer approximation in agreement was obtained using the Harrington equation (based on BMI, age and gender). The equations using variables, such as weight, height, age and gender demonstrated higher agreement than the equations using merely weight and gender. Higher educational level was associated with normal weight, while higher calorific ratio was found in the class of normal-weighted individuals. An inverse relationship between ΒΜΙ and RMR was also observed and a logarithmic equation for calculating RMR was created, which was differentiated in relation to BMI classes, using the weight and gender variables. CONCLUSION: A better measurement agreement between RMR prediction equations and IC may be achieved due to BMI consideration. The present findings contributed to a better understanding of the measured parameters, confirming the inverse relationship between BMI and RMR. Age group and gender variables may also exert significant role on the bias response of some RMR equations.

Advanced small cell lung cancer (SCLC): new challenges and new expectations.

Small cell lung cancer (SCLC) remains one of the most lethal malignancies and a major health riddle. The therapeutic options are limited. The combination of etoposide or irinotecan with platinum chemotherapy is the standard of care at any stage. The last decade systemic efforts have been done to reveal specific therapeutic targets for small cell lung carcinomas. In this review, we focus on the new therapeutic strategies of SCLC, including immune-related treatment that may change the prognosis of the disease. The main genetic mutations observed in SCLC are TP53 and RB1 mutations; however, it is well known that these molecules are not yet targetable. In recent years, research has revealed other frequent genetic alterations and activated signaling pathways that might be an effective treatment target. Loss of PTEN, activating PI3K mutations, inhibition of NOTCH pathway and aurora kinase activation are among them. Moreover, FDGFR1 amplification, activation of the Hedgehog pathway and repair-protein PARP1 seem to participate in SCLC tumorigenesis. These new findings have identified some interesting targets. Moreover, immunotherapy tries to find its place in the treatment of SCLC. Immune checkpoint inhibitors are under investigation in phase I to III clinical trials. We hope that in next years the treatment of SCLC patients will be improved with the administration of targeting therapy and the introduction of immunotherapy.

Advances on systemic treatment for lung neuroendocrine neoplasms.

Lung well-to-moderately differentiated neuroendocrine tumors (also known as carcinoids) and large cell neuroendocrine lung carcinoma (poorly differentiated neuroendocrine tumor) are rare neuroendocrine neoplasms, which account for less than 4% of all lung neoplasms. Due to their low incidence, their systemic treatment is greatly influenced by therapeutic evidence derived from the more frequent gastroenteropancreatic neuroendocrine neoplasms and/or small cell lung carcinoma leading to significant bias. Currently, employed systemic therapies for lung carcinoids, aiming at controlling tumor growth include long acting somatostatin analogues (SSAs), peptide receptor radionuclide therapy, chemotherapy and molecular-targeted therapy. In this review, each of those treatments is presented based upon available clinical evidence from retrospective and prospective studies particularly focused on the role of everolimus in the advanced setting and on ongoing clinical trials reflecting our expectations in the near future. In addition, we critically analyse currently employed treatment of large cell neuroendocrine carcinoma where the appropriate chemotherapeutic regimen is still a matter of debate.