Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.

Signal intensity changes of dentate nucleus on plain MR T1WI innasopharyngeal carcinoma patients after radiotherapy andmultiple injections of gadolinium-base contrast agent

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Hyoid metastasis an unusual location from lung cancer

Bone metastases from lung cancer account for 8.5%,with those located in the hyoid bone being extremely rare.In this editorial,we made a review about Hsu et al case report highlighted the importance of palliative radiotherapy,even with an unusual but effective scheme in pain control in a patient with non-small cell lung cancer in stage IV.

The Inhibitory Effects of Rh-endostatin(YH-16) in Combination with Radiotherapy on Lung Adenocarcinoma A549 in Mice and the Underlying Mechanisms

In order to investigate the inhibitory effects of Endostar(rh-endostatin,YH-16)in combination with radiotherapy on lung adenocarcinoma A549 in mice and the interaction mechanisms of combined therapy,the transplantation tumor models of A549 lung adenocarcinoma were established.When the largest diameter of tumor reached 1.0cm,all nude mice were randomly divided into 4 groups:Endostar group,radiotherapy group,radiotherapy plus Endostar(combined treatment)group,and control group(n=6 in each group).The largest d...

Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy

Background: Locoregional recurrence remains the challenge for long-term survival of non-small cell lung cancer(NSCLC) patients after radical surgery, and curative-intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical radiotherapy.Methods: We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat-sen University Cancer Center(Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to identify prognostic factors.Results: Grade 3/4 adverse events included neutropenia(8 cases, 10.8%), esophagitis(7 cases, 9.5%), pneumonitis(1 case, 1.4%), and vomiting(1 case, 1.4%).The 2-year overall survival, progression-free survival, local recurrencefree survival(LRFS), and distant metastasis-free survival(DMFS) rates of all patients were 84.2,42.5,70.0, and 50.9%,respectively. Univariate and multivariate analyses showed that a higher biological effective dose(BED) of radiation was associated with longer LRFS [hazard ratios(HR)=0.317,95% confidence interval(CI) = 0.112-0.899, P = 0.016] and that wild-type epidermal growth factor receptor(EGFR) was associated with longer DMFS compared with EGFR mutation(HR = 0.383,95% CI=0.171-0.855, P = 0.019).Conclusions: Radical radiotherapy is effective and well-tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild-type EGFR is a predictor for long DMFS.

Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer:A Case Report

Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein 1(PD-1)inhibitor,blocks T cells activation preventing signal and allows the immune system to clear cancer cells.Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA,with less than 10%unusual skin reaction,like sensory neuropathy,peeling skin,erythema multiforme,vitiligo,and psoriasis.Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity.The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies,but the risk of side effects may be high.We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy.The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events.Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

The Clinical Usefulness of ^(99m)Tc-Tetrofosmin Scintigraphy in the Diagnosis of Lung Neoplasmas and Mediastinal Lymphoid Node Involvement

In order to investigate the clinical significance of 99mTc-Tetrofosmin （TF） scintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmo- nary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target （T/N） ratio between the lung cancer group and the benign lesion group （P〈0.001）. Moreover, in the lung cancer group, T/N ratio in tomographies was signifi- cantly higher than that in planar images （P〈0.01）. The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas （P〈0.05 and P〈0.01 respectively）, so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinal lymphoid node metastasis （P〈0.05）. It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas （P〈0.05）, and 2 h washout rate （WR） of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas （P〈0.05）. In conclusion, 99mTc-TF scintigraphy showed a favorable diag- nostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer.

Progress in image-guided radiotherapy for the treatment of non-small cell lung cancer

Lung cancer is one of the most common malignant tumors. It has the highest incidence and mortality rate of all cancers worldwide. Late diagnosis of nonsmall cell lung cancer(NSCLC) is very common in clinical practice, and most patients miss the chance for radical surgery. Thus, radiotherapy plays an indispensable role in the treatment of NSCLC. Radiotherapy technology has evolved from the classic two-dimensional approach to three-dimensional conformal and intensity-modulated radiotherapy. However, how to ensure delivery of an accurate dose to the tumor while minimizing the irradiation of normal tissues remains a huge challenge for radiation oncologists, especially due to the positioning error between fractions and the autonomous movement of organs. In recent years, image-guided radiotherapy(IGRT) has greatly increased the accuracy of tumor irradiation while reducing the irradiation dose delivered to healthy tissues and organs. This paper presents a brief review of the definition of IGRT and the various technologies and applications of IGRT. IGRT can help ensure accurate dosing of the target area and reduce radiation damage to the surrounding normal tissue. IGRT may increase the local control rate of tumors and reduce the incidence of radio-therapeutic complications.

Analysis of the Long-term Effect of Intraoperative Radiotherapy (IORT) for Non-Small Cell Lung Carcinoma (NSCLC)

OBJECTIVE To analyze the long-term effects of treatment with an op-eration + postoperative irradiation (A group) and an operation+intraoperative radiotherapy+postoperative irradiation (B group) in non-small cell lung cancer patients. METHODS Through a prospective randomized clinical trial, a total of 154 patients with non-small cell lung carcinoma were divided into two groups of 77 cases. Among the 154 cases, there were 134 squamous carcinomas, 17 adenocarcinomas and 3 adeno-squamous carcinomas. TNM staging: there were 17 in StageⅠ, 76 in Stage Ⅱ and 61 in Stage Ⅲ. A dosage of 15～25 Gy IORT, energy 9～16 MeV electrons, was delivered to the tumors. The doses given were 40～60 Gy postoperation. RESULTS The local control rates in A and B groups were 49.4% and 62.3% respectively (P<0.05). The survivals at 3, 5 and 7 years for group A were 40.3%, 27.3%, and 5.2% and for group B 44.2%, 28.6% and 6.5% (P>0.05). There were 16 deaths from radiotherapy complications, with 2 cases in group A and 14 in group B. CONCLUSION IORT+postoperative irradiation can enhance the local control rate of non-small cell lung cancer patients and reduce the recurrent rates, but it can not improve long-term survival.

Phase Ⅰ/Ⅱ study of gemcitabine and oxaliplatin chemotherapy in combination with concurrent 3-D conformal radiotherapy for locally advanced non-small cell lung cancer

Background and objective Recent studies have showed that combination of chemotherapy and radiotherapy might result in better outcome for locally advanced non-small cell lung cancer (NSCLC). The aim of this study is to determine the maximal tolerance dose (MTD) and efficacy of full-dose gemcitabine and oxaliplatin when given concurrently with 3-dimentional radiation therapy (3D-RT) for locally advanced NSCLC. Methods Oxaliplatin was administered at a fixed dose of 130mg/m^2, and gemcitabine was administered at a starting dose of 800mg/m^2 with an incremental dose gradient of 200mg/m^2 for 3 dose levels. MTD was defined as the immediate dose level lower than the dose at which dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered at 3-week cycle. The RT was given as 3-D conformal manner at a single daily dose of 2Gy for 5 days per week. Results Twenty-two patients were evaluable and distributed to three different dose levels: 6 at level 1, 8 at level 2 and 8 at level 3. Pulmonary toxicity, esophageal and hematologic toxicity were the main DLT. Grade Ⅲ acute pulmonary toxicity occurred in one patient each at level 2 and level 3, both with V20>20%, and grade Ⅲ esophagitis in two patients at level 3. The MTD of gemcitabine in this study was 1000mg/m^2. The overall response rate was 75.0% (9/12). The 1- and 2-year survival rate was 70.0% and 30.5% respectively. The median time to progression was 8.7 months (range 5--11.8 months). Conclusion With reduced radiation volume, gemcitabine of 1000mg/m^2 in combination with oxaliplatin of 130mg/m^2 was effective and could be safely administered for NSCLC.

Partial and Full Arc Volumetric Modulated Arc Therapy in Lung Cancer Stereotactic Body Radiotherapy with Different Definitions of Internal Target Volume Based on 4D CT

Purpose: To investigate the feasibility of partial arc volumetric modulated arc therapy (VMAT) in lung cancer stereotactic body radiotherapy (SBRT), as well the volumetric and dosimetric effects of different internal target volume (ITV) definitions with 4D CT. Methods: Fourteen patients with primary and metastatic lung cancer underwent SBRT were enrolled. Full and partial arc VMAT plans were generated with four different ITVs: ITVall, ITVMIP, ITVAIP and ITV2phases, representing ITVs generated from all 10 respiratory phases, maximum intensity projection (MIP), average intensity projection (AIP), and 2 extreme respiratory phases. Volumetric and dosimetric differences, as well as MU and delivery time were investigated. Results: Partial arc VMAT irradiated more dose at 2 cm away from planning target volume (PTV) (P = 0.002), however, it achieved better protection on mean lung dose , lung V5, spinal cord, heart and esophagus compared with full arc VMAT. The average MU and delivery time of partial arc VMAT were 240 and 1.6 min less than those of full arc VMAT. There were no significant differences on target coverage and organ at risks (OARs) sparing among four ITVs. The average percent volume differences of ITVMIP, ITVAIP and ITV2phases to ITVall were 8.6%, 13.4%, and 25.2%, respectively. Conclusions: Although partial arc VMAT delivered more dose 2 cm out of PTV, it decreases the dose to lung, spinal cord, and esophagus, as well decreased the total MU and delivery time compared with full arc VMAT without sacrificing target coverage. Partial arc VMAT was feasible and more efficient for lung SBRT.

End of Life Experience of Symptom Cluster and Their Management in Hong Kong Chinese Patients with Lung Cancer Who Receive Palliative Radiotherapy

Breathlessness, fatigue, and anxiety are distressing symptoms for patients with advanced lung cancer, however, they are not relieved by palliative RT and are often viewed as neglected areas of clinical practice. This paper aims to review def initions of, and explore patients' experiences of, breathlessness, fatigue, and anxiety. Further, it will outline existing approaches, both pharmacological and non-pharmacological, to treat them. Current treatments and perceptions of these symptoms will be discussed in the context of Hong Kong health care service. The review of literature also shows that breathlessness, fatigue and anxiety appears to have similar emotional origins. A contemporary approach of using a common pyschoeducational intervention to treat these symptoms together as a cluster in end of life care will be discussed.

Factors influencing comfort level in head and neck neoplasm patients receiving radiotherapy

Objective:To determine factors that influence comfort in head and neck neoplasm patients receiving radiotherapy.Methods:In total,200 head and neck neoplasm patients receiving radiotherapy were recruited from three tertiary first class hospitals.They were assessed by Radiotherapy Comfort Questionnaire for patients with head and neck neoplasm,Social Support Scale,and Medical Coping Modes Questionnaire.Results:The total score of comfort was 60.54±8.32.Multiple linear regression analysis indicated that number of radiation treatments,family accompaniment,educational level,resignation coping mode,complications due to diabetes,accompanying chemotherapy,and the utilization of social support significantly influenced comfort level(p<0.05).Among these,number of radiation treatments,complications due to diabetes,accompanying chemotherapy,and resignation coping were negative factors.Conclusion:Encouraging utilization of social support systems and a positive coping mode is important for increasing comfort level in head and neck neoplasm patients during radiotherapy.Nurses should pay particular attention to those patients during later stages of radiotherapy or chemotherapy,with diabetes,without family accompaniment,and with lower education level.

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report

BACKGROUND Despite being the most common intraocular malignancy among adults,choroidal melanoma is a rare cancer type,even more so when accompanied by lung cancer.We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy(CIRT).CASE SUMMARY A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye.During the examination,we found a right lung tumor that was histologically diagnosed as lung cancer.The patient was treated with CIRT for both malignant neoplasms.The CIRT dose was 70 photon equivalent doses(GyE)in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer.At 3 mo after CIRT,the choroidal melanoma completely disappeared,as did the right lung cancer 7 mo after;the patient was in complete remission.CONCLUSION CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

Clinical analysis of concurrent chemoradiotherapy in 83 patients with locally advanced non-small cell lung cancer

Objective:The purpose of this study was to evaluate the efficacy and safety of concurrent chemoradiotherapy (CCRT) in patients with locally advanced non-small cell lung cancer (LANSCLC). Methods:83 cases of patients who have been diagnosed for locally advanced NSCLC by determined cytology or pathology were divided into two groups randomly, 42 patients in NP group and 41 patients in EP group. All patients accepted thoracic three-dimensional conformal radiotherapy (3D-CRT) and concurrent either NP chemotherapy in NP group or EP chemotherapy in EP group. 3D-CRT were started on day 1 in the first cycle of chemotherapy. Chemotherapy were carried out for 4 cycles, every cycle was 21 days. Thoracic radiotherapy adopted conventional fractionated irradiation with 15 MeV-X ray, a total dose of 60 Gy. Results: In 83 patients were evaluable, there were 5 cases complete regression to be observed, 29 cases had partial regression (PR), 7 cases with stable disease (SD) and 1 case with progression disease (PD) in NP group. CR 3 cases, PR 27 cases, SD 9 cases and PD 2 cases in EP group. The overall response rate (RR) both NP group and EP group were 80.9%, 73.2%, respectively (P = 0.785).1-, 2-, 3-year survival rate were 90.5%, 69.0%, 28.6% and 82.9%, 51.2%, 21.9%, respectively (P = 0.393). The incidence of leukopenia and thrombocytopenia in NP group was higher than that in the EP group (P < 0.05). Conclusion:CCRT in patients with locally advanced non-small cell lung cancer, 3D-CRT with concurrent NP or EP chemotherapy. 1-, 2-, 3-year overall survival (OS) and average survival time (AST) were not statistically differences, a higher incidence of toxicities were observed in NP group but can be tolerable.

Dosimetric Impact of Tumor Position and Lung Density Variations in Lung Stereotactic Body Radiotherapy

Purpose of this study was to evaluate the variation of the dose to gross tumor volume (GTV) related to tumor position and lung density for lung stereotactic body radiotherapy (SBRT) using a virtual phantom. The density of the equivalent lung surrounding the GTV (10 mm diameter) was defined as 0.10, 0.15, 0.25, 0.35, and 0.45 g/cm3. A planning target volume (PTV) was generated by adding a uniform 8 mm margin to the internal target volume (ITV). We defined that the 99% of the GTV should be covered by 100% of the prescribed dose using Monte Carlo (MC) calculation. The GTV structure was replicated from ITV to the PTV periphery at 1 mm intervals. Planned dose to the GTV was defined as the predicted dose in the replicated GTV structure. Simulated dose to the GTV was defined as the calculated dose in the replicated GTV structure taking into account the tumor position error. D99 of the planned dose to the GTV at the 8 mm shift position was 78.1%, 81.6%, 87.3%, 91.4% and 94.4% at equivalent lung densities of 0.10, 0.15, 0.25, 0.35, and 0.45 g/cm3, respectively. D99 of the simulated dose to the GTV at the 8 mm shift position was 96.9%, 95.3%, 94.2%, 95.1 % and 96.3% at equivalent lung densities of 0.10, 0.15, 0.25, 0.35, and 0.45 g/cm3, respectively. Planned dose to GTV is strongly dependent on lung density and tumor position errors, while simulated dose to GTV does not show any significant dependence.

Is there a place for optimizing thoracic radiotherapy in limited-stage small cell lung cancer after twenty years?

Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.