Search Results (25)

The current standard of care for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemotherapy and radiation therapy with consolidation durvalumab. Despite this approach, about 50% of patients will experience disease recurrence, with about half of recurrence events occurring at distant metastatic sites. In this review, the authors performed a structured analysis of the available clinical trial data and literature related to the treatment of this disease. The authors discuss the detriments and merits of several of these trials and explore clinical and preclinical data that contribute to the growing body of literature supporting a future with new approaches, including new techniques in radiation therapy, sequencing, and agents. Upcoming trials may illuminate a path towards better outcomes for patients in this setting. Full article

Background and Objectives: The comparative efficacy and safety of nivolumab plus ipilimumab (Nivo-Ipi) combination therapy between patients with either postoperative recurrent non-small cell lung cancer (NSCLC) or inoperable stage III/IV NSCLC have yet to be conclusively determined. Materials and Methods: This retrospective study reviewed the medical records of consecutive patients diagnosed with either postoperative recurrent NSCLC or inoperable stage III/IV NSCLC. Both groups, referred to as the postoperative and inoperable cohorts respectively, underwent Nivo-Ipi therapy at four Japanese medical institutions between December 2020 and November 2022. The study’s primary aim was to evaluate and compare the efficacy and safety outcomes across these two groups. Results: A total of 161 patients received Nivo-Ipi therapy (postoperative group, n = 30; inoperable group, n = 131). The objective response rate was comparable between the postoperative and inoperable groups (36.7% vs. 32.1%, p = 0.67). Median progression-free survival did not differ significantly between groups (8.9 months vs. 6.5 months, p = 0.14). However, median overall survival was significantly longer in the postoperative group (not reached vs. 13.0 months, p = 0.012). The incidence of grade ≥ 3 adverse events in the postoperative group included lung injury (13.3%), liver dysfunction (10.0%), adrenal insufficiency (6.7%), and colitis (6.7%). No significant difference was observed in the frequency of grade ≥ 3 treatment-related adverse events between the groups, and no treatment-related deaths occurred in the postoperative group. Conclusions: Patients with postoperative recurrent NSCLC treated with Nivo-Ipi demonstrated significantly longer overall survival compared to those with inoperable NSCLC. Given its favorable efficacy and acceptable toxicity profile, postoperative recurrent disease may warrant consideration as a stratification factor in clinical trials for advanced NSCLC. Nivo-Ipi therapy could serve as a preferred first-line treatment option for patients with postoperative recurrent NSCLC. Full article

Background/Objectives: Patients with stage III non-small cell lung cancer represent a very heterogeneous group of patients. In the past, the standard of care for patients with inoperable stage III non-small cell lung cancer was concurrent or sequential radical radiotherapy and chemotherapy. But the progression-free survival was 8 months, and the 5-year overall survival rate was less than 20%. After the results of the PACIFIC study, the standard of care for this group of patients is chemoradiotherapy with durvalumab as consolidation therapy. The aim of our study was to evaluate the efficacy of consolidation durvalumab in a real-world setting after sequential CRT. Methods: We included 24 patients with unresectable stage III non-small cell lung cancer who did not progress after sequential chemoradiotherapy and who received durvalumab consolidation. Results: Median progression-free survival was 16 months, 95% CI (0.5–31.5), and median overall survival was 20 months, 95% CI (13.4–26.6 months). The twelve-month progression-free survival and overall survival rate were 55.1% and 68%, respectively, and the 18-month progression-free survival and overall survival rates were 44.1% and 56.5%, respectively. Conclusions: Durvalumab introduced a new era in the treatment of patients with unresectable stage III non-small cell lung cancer with a significantly prolonged 5-year overall survival rate. Our study is one of the few that investigated the efficacy of durvalumab in a real-world setting after sequential CRT. Our results showed that durvalumab is effective in patients who were treated with sequential CRT. However, the time between radiotherapy termination and the start of durvalumab should be shorter. Full article

The standard of care for early-stage NSCLC has historically been surgical resection. Given the association of lung cancer with smoking, a large number of early-stage patients also have active smoking-related medical comorbidities such as COPD precluding surgery. The current approach for treating such inoperable patients is frequently considered to be stereotactic body radiation therapy (SBRT). SBRT (also known as stereotactic ablative radiation therapy or SABR) is a curative modality that precisely delivers very high dose radiation in few (typically <5) sessions. That said, because of their minimal invasiveness and repeatable nature, image-guided thermal ablation therapies such as radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CA) have also been used to treat early-stage lung tumors. For those patients deemed to have “high operative risk” (i.e., those who cannot tolerate lobectomy, but are candidates for sublobar resection), the appropriateness of potential alternatives [e.g., SBRT; ablation] to surgery is an active area of investigation. In the absence of completed randomized phase III trials, the approach to comparing outcomes between surgery, SBRT, or ablative therapies by their efficacy or equivalence is complex. An overview of the role of SBRT and other non-surgical modalities in the management of early-stage lung cancer is the subject of the present review. Full article

Stereotactic body radiotherapy has been established as a viable treatment option for inoperable early-stage non-small cell lung cancer or secondary lesions mainly in oligoprogressive/oligometastatic scenarios. Treating lesions in the so-called “no flight zone” has always been challenging and conflicting data never cleared how to safely treat these lesions. This is truer considering ultra-central lesions, i.e., directly abutting or whose PTV is overlapping critical mediastinal organs. While historical retrospective data are abundant but mostly heterogenous in terms of the definition of ultra-central lesions, dosing regimens and outcomes, prospective data remain scarce, even though recently published studies have given new encouraging results for such delicate treatment scenarios. For this reason, we aimed to review and summarize current knowledge on stereotactic radiation treatment for ultra-central thoracic lesions, highlighting the most recent advances and the messages that can be taken from them. Lastly, we propose a workflow of the necessary steps to identify and treat such patients, therefore helping in elucidating the advantages and caveats of such treatment options. Full article

Using digitized data from progression-free survival (PFS) and overall survival Kaplan–Meier curves, one can assess population survival kinetics through exponential decay nonlinear regression analyses. To demonstrate their utility, we analyzed PFS curves from published curative-intent trials of non-small cell lung cancer (NSCLC) adjuvant chemotherapy, adjuvant osimertinib in resected EGFR-mutant NSCLC (ADAURA trial), chemoradiotherapy for inoperable NSCLC, and limited small cell lung cancer (SCLC). These analyses permit assessment of log–linear curve shape and estimation of the proportion of patients cured, PFS half-lives for subpopulations destined to eventually relapse, and probability of eventual relapse in patients remaining progression-free at different time points. The proportion of patients potentially cured was 41% for adjuvant controls, 58% with adjuvant chemotherapy, 17% for ADAURA controls, not assessable with adjuvant osimertinib, 15% with chemoradiotherapy, and 12% for SCLC. Median PFS half-life for relapsing subpopulations was 11.9 months for adjuvant controls, 17.4 months with adjuvant chemotherapy, 24.4 months for ADAURA controls, not assessable with osimertinib, 9.3 months with chemoradiotherapy, and 10.7 months for SCLC. For those remaining relapse-free at 2 and 5 years, the cure probability was 74%/96% for adjuvant controls, 77%/93% with adjuvant chemotherapy, 51%/94% with chemoradiation, and 39%/87% with limited SCLC. Relatively easy population kinetic analyses add useful information. Full article

Lung cancer is the leading cause of cancer-associated death globally. Staging provides classification of the anatomic extent of cancer that is used consistently worldwide. Lung cancer staging is necessary for prognostication, to inform treatment options, and to allow accurate representation in clinical trials. Staging also separates operable from inoperable disease. Since its introduction in the 1970s, the Tumor, Node and Metastasis (TNM) Staging System has undergone significant revisions, with the latest version, the eighth edition, being effective internationally since 2017. Advances in bronchoscopic and thoracoscopic technologies have expanded procedures to diagnose lung cancer and accurately define the anatomic stage. Understanding the advantages and disadvantages of available methods for staging lung cancer is critical to clinician decision making. In patients with lung cancer without distant metastases, the staging of mediastinal lymph nodes determines treatment options. To minimize the risk and cost, the most appropriate method of staging should identify the highest disease stage while carrying acceptable risk. Minimally invasive endoscopic needle techniques to stage the mediastinum are the first choice to assess for metastases in accessible lymph node stations. Surgical techniques are generally reserved for specific clinical situations, including following negative endoscopic needle techniques when suspicion for nodal involvement is high and to assess endoscopically inaccessible lymph nodes. This review provides a concise account of TNM staging of non-small cell lung cancer (NSCLC) and overview of procedures available for the staging of lung cancer. Full article

The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006–2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments. Full article

Introduction: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in cancer patients, occurring most frequently in patients with small cell lung cancer. However, this syndrome occurs extremely rarely in patients with non-small cell lung cancer. The results of the clinical trials have revealed that immuno-oncological therapies are effective for long periods of time, providing hope for long survival and with a good quality of life. Case Presentation: We present the case of a female patient who was 62 years old at the time of diagnosis in 2016 who underwent surgery for a right pulmonary tumor (pulmonary adenocarcinoma) and subsequently underwent adjuvant chemotherapy. The patient had a left inoperable mediastinohilar relapse in 2018, which was treated using polychemotherapy The patient also had an occurrence of progressive metastasis and a syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 2019 for which immunotherapy was initiated. The patient has continued with immunotherapy until the time this study began to be written (April 2023), the results being the remission of hyponatremia, the clinical benefits and long-term survival. Discussion: The main therapeutic option for SIADH in cancer patients is the treatment of the underlying disease, and its correction depends almost exclusively on a good response to oncological therapy. The initiation of immunotherapy at the time of severe hyponatremia occurrence led to its remission as well as the remission of the other two episodes of hyponatremia, which the patient presented throughout the evolution of the disease, demonstrating an obvious causal relationship between SIADH and the favorable response to immunotherapy. Conclusions: Each patient must be approached individually, taking into account the various particular aspects. Immunotherapy proves to be the innovative treatment that contributes to increasing the survival of patients with metastatic non-small cell lung cancer and to increasing their quality of life. Full article

Background: Consolidation systemic therapy (ST) given after concurrent radiotherapy (RT) and ST (RT-ST) is frequently practiced in locally advanced inoperable nonsmall cell lung cancer (NSCLC). Little is known, however, about the fate of patients achieving different responses after concurrent phases of the treatment. Methods: we searched the English-language literature to identify full-length articles on phase II and Phase III clinical studies employing consolidation ST after initial concurrent RT-ST. We sought information about response evaluation after the concurrent phase and the outcome of these patient subgroups, the patterns of failure per response achieved after the concurrent phase as well as the outcome of these subgroups after the consolidation phase. Results: Eighty-seven articles have been initially identified, of which 20 studies were excluded for various reasons, leaving, therefore, a total of 67 studies for our analysis. Response evaluation after the concurrent phase was performed in 36 (54%) studies but in only 14 (21%) response data were provided, while in 34 (51%) studies patients underwent a consolidation phase regardless of the response. No study provided any outcome (survivals, patterns of failure) as per response achieved after the concurrent phase. Conclusions: Information regarding the outcome of subgroups of patients achieving different responses after the concurrent phase and before the administration of the consolidation phase is still lacking. This may negatively affect the decision-making process as it remains unknown which patients may preferentially benefit from the consolidation of ST. Full article

Background and Objectives: Stereotactic ablative radiotherapy (SABR) is not confined to early stage non-small cell lung cancer (NSCLC) and has a potential role in stage IV disease. We aimed to evaluate the effect of SABR on local control rates and survival outcomes in patients with all stages of NSCLC according to the treatment aim. Materials and Methods: We retrospectively reviewed the medical records of 88 patients with NSCLC who received SABR at the Korea University Guro Hospital between January 2015 and March 2021. Among these, 64 patients with stage I–II NSCLC ineligible for surgery were treated with a definitive aim. Twenty-four patients with stage IV limited metastatic NSCLC showing a favorable response to prior systemic therapy were treated with a consolidative aim. Results: The median follow-up time was 34 (range: 5–88) months. Thirty-one patients developed recurrence (35.2%), with distant metastasis being the most common (25/31, 80.6%). In-field local recurrence occurred in four patients (4/88 patients, 4.5%). For patients treated with definitive SABR, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 91.8% and 58.6%, respectively. In patients treated with consolidative SABR, the 3-year OS and DFS rates were 86.7% and 53.8%, respectively. With respect to treatment-related pulmonary toxicity, grade 3 radiation pneumonitis incidence requiring hospitalization was 2.3% (2/88). Conclusions: Definitive SABR is appropriate for medically inoperable or high surgical risk patients with early stage NSCLC with acceptable treatment-related toxicities. Consolidative SABR improves local control rates and helps achieve long-term survival in patients with limited metastatic NSCLC. Full article

Stereotactic body radiation therapy (SBRT) has been widely adopted as an alternative to lobar resection in medically inoperable patients with lymph-node negative (N0) early-stage (ES) non-small cell lung cancer (NSCLC). Excellent in-field local control has been consistently achieved with SBRT in ES NSCLC ≤ 3 cm in size. However, the out-of-field control following SBRT remains suboptimal. The rate of recurrence, especially distant recurrence remains high for larger tumors. Additional systemic therapy is warranted in N0 ES NSCLC that is larger in size. Radiation has been shown to have immunomodulatory effects on cancer, which is most prominent with higher fractional doses. Strong synergistic effects are observed when immune checkpoint inhibitors (ICIs) are combined with radiation doses in SBRT’s dose range. Unlike chemotherapy, ICIs can potentiate a strong systemic response outside of the irradiated field when combined with SBRT. Together with their less toxic nature, ICIs represent a very suitable class of systemic agents to be combined with SBRT when treating ES NSCLC with high-risk features, such as larger tumor size. In this review, we describe the rationale and emerging evidence, as well as ongoing investigations in this area. Full article

Background: We report the outcomes for unresectable patients with locally advanced or oligometastatic non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) or immunotherapy who achieved a clinical downstaging so as to re-enter resectability. Methods: We retrospectively reviewed the clinical, surgical, and pathological data of 42 patients with histologically proven, inoperable NSCLC who received rescue surgery after a good response to TKI or immunotherapy between March 2014 and December 2021. Results: Of 42 patients, 39 underwent pulmonary resection with therapeutic intent (three explorative thoracotomies). There were 26 males, with a median age of 64 years (range, 41–78 years). Twenty-three patients received TKIs and 19 immunotherapies. Anatomic resection was performed in 97.4% of resected patients (38/39) including 30 lobectomies, one right upper sleeve lobectomy, five pneumonectomies, one tracheal sleeve pneumonectomy, and one bilobectomy; a patient underwent wedge resection. Of 10 procedures attempted via a robotic approach, two required conversion to thoracotomy. No intraoperative morbidity/mortality occurred. The median operative time was 190 (range, 80–426) minutes; estimated blood loss was 200 mL (range, 35–780 mL). Morbidity occurred in 13/39 (33.3%). The median length of hospital stay was 6.5 days (range, 4–23 days). Pathologic downstaging was 74.4% (29/39). With a median follow-up of 28.7 months, the 5-year disease-free interval was 46.5%, and the 5-year overall survival was 66.0%; 32/39 patients (82.1%) are alive, 10 with the disease. Conclusions: Lung resection for suspected residual disease after immunotherapy or TKIs is feasible, with encouraging pathological downstaging. Surgical operation may be technically challenging due to the presence of fibrosis, but significant morbidity appears to be rare. Outcomes are encouraging, with reasonable survival during the short-interval follow-up. Full article

Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process. Full article

Background: Maintenance treatment with immune-checkpoint inhibition (ICI) has been shown to significantly improve patient prognosis after chemoradiotherapy (CRT) for inoperable stage III NSCLC. This survival advantage may be achieved at the expense of an increased probability for symptomatic pneumonitis as CRT as well as ICI treatment is associated with the risk of treatment-related pulmonary toxicity. Methods: We screened a prospective chemoradioimmunotherapy (CRT-IO) cohort consisting of 38 patients and identified patients with therapy-related grade 3 pneumonitis. All patients were treated with intravenous high dose corticosteroids and closely monitored by CT-scans and extended longitudinal lung function tests. We analyzed lung function parameters and CT morphological features to characterize patients’ outcome. Results: Six (16%) patients treated with CRT-IO developed grade 3 pneumonitis one to six months after completion CRT. In the CT imaging, pneumonitis was characterized by diffuse ground glass capacities and in part pulmonary consolidations within and outside the planning target volume. Onset of pneumonitis was accompanied by a reduction in diffusion capacity in all cases. The mean decline of diffusion capacity was 25.8% [6–53%]. Under treatment with corticosteroids, all patients recovered regarding symptoms and changes in CT morphology. In five out of six patients, diffusion capacity improved to at least 80% of the baseline [80–96%]. One patient showed a significant increase of diffusion capacity after treatment (from 32% to 53%) but reached only 62% of the initial value. Conclusions: Pneumonitis is a severe complication of CRT-IO. High-resolution CT imaging and extended lung function testing proved to be a suitable approach in detecting and monitoring of CRT-IO associated pneumonitis. Full article