Definitive Concurrent Chemotherapy Research Articles

Locally Advanced Cervical Cancer: Neoadjuvant Treatment versus Standard Radio-Chemotherapy-An Updated Meta-Analysis.

The treatment of choice for patients with locally advanced cervical cancer (LACC) is definitive concurrent radio chemotherapy which consists of external beam radiotherapy (EBRT) and concurrent platinum-based chemotherapy (CCRT), with the possible addition of brachytherapy (BT). However, the benefits of adjuvant surgery after neoadjuvant treatments remain a debated issue and a still open question in the literature. This meta-analysis aims to provide an updated view on the controversial topic, focusing on comparing surgery after any adjuvant treatment and standard treatment. Following the recommendations in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, the PubMed and Embase databases were systematically searched in April 2023 for early publications. No limitations on the country were applied. Only English articles were considered. The comparative studies containing data about disease-free survival (DFS) and/or overall survival (OS) were included in the meta-analysis. The CCRT + surgery group showed a significantly better DFS than CCRT (RR 0.69 [95% CI 0.58-0.81] p < 0.01) and a better OS (RR 0.70 [95% CI 0.55-0.89] p < 0.01). Nine studies comparing neoadjuvant chemotherapy (NACT) plus surgery and CCRT were also enrolled. The NACT + surgery group showed a significantly better DFS than CCRT (RR 0.66 [95% CI 0.45-0.97] p < 0.01) and a better OS (RR 0.56 [95% CI 0.38-0.83] p < 0.01). In the sub-analysis of three randomized control trials, the surgery group documented a non-significantly better DFS and OS than CCRT (OR 1.10 [95% CI 0.67-1.80] p = 0.72; I2 = 69% p = 0.72; OR 1.09 [95% CI 0.63-1.91] p = 0.75; I2 = 13% p = 0.32). The results provide updated findings about the efficacy of neoadjuvant treatments, indicating significantly improved DFS and OS in patients undergoing hysterectomy after CCRT or NACT compared with patients undergoing standard treatments.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma

IntroductionAdjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. Materials and methodsWe analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. ResultsMedian age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). ConclusionThis study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.

Long-Term Outcomes and Toxicity in Esophageal Cancer Patients after Neoadjuvant or Definitive Concurrent Chemotherapy with Proton Beam Therapy

Proton-beam therapy (PT) is increasingly utilized over three dimensional-conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) photon irradiation for the treatment of various malignancies due to better toxicity reduction. We investigated the long-term outcomes and toxicity in esophageal cancer (EC) patients treated with PT as part of their neoadjuvant concurrent chemoradiation followed by surgery (nCRT) or definitive concurrent chemoradiation (dCRT) treatment regimen. All consecutively treated, American Joint Committee on Cancer 7th edition clinical stage I-IV EC patients from 2006 to 2022 were retrospectively analyzed. Standard RT dose for most patients was 50.4 Gy/28 fractions. nCRT patients had surgery within 4 months post-RT. Kaplan-Meier method was used to determine overall survival (OS), locoregional recurrence-free survival (LRRFS) and distant metastatic-free survival (DMFS). Acute and chronic RT-related toxicities were graded with Common Terminology Criteria for Adverse Events version 4.0. There were 510 EC PT patients: 204 (40%) had nCRT and 306 (60%) had dCRT. Most lesions were located in the lower esophagus, of adenocarcinoma histology and treated with passive scatter PT. Overall median follow-up was 72 months. Median, 3- and 5-year OS for all patients were 43 months, 54.1% and 44.9%, respectively. Median LRRFS and DMFS were not reached. Esophagitis was the most common grade ≥3 (G3+) toxicity (59 patients; 28.9%, including a G4 and a G5 toxicity), followed by nausea (29 patients; 14.2%) and esophageal stricture (26 patients, 12.7%). With nCRT, median, 3- and 5-year OS were 80 months, 64.7% and 56.1%, respectively, while the median LRRFS and DMFS were not reached again. Their most common G3+ toxicity was esophagitis in 14 patients (6.9%) followed by nausea (8 patients; 3.9%). An nCRT patient developed G4 RT pneumonitis. Pathological complete response (pCR) was observed in 58 patients (28.4%). Surgery-related pulmonary, cardiac and gastrointestinal complications were reported in 38 (18.6%), 40 (19.6%) and 43 (21.1%) patients, respectively. dCRT patients had a median follow-up of 65 months, and median, 3- and 5-year OS of 32 months, 46.7% and 37.0%, respectively. Although the median LRRFS was not reached, the median DMFS was 74 months. The most observed dCRT G3+ toxicity was esophagitis (45 patients, 22.1%: including both G4 and G5 patients) and then esophageal stricture (23 patients, 11.3%). A dCRT patient developed G4 fistula. To our knowledge, this is the largest single-institutional study on EC long-term outcomes and toxicity using PT. Our cohort reveals good outcomes and mostly mild CRT-related toxicities. Trimodality nCRT with protons demonstrates excellent outcomes relative to the CROSS trial (49.4 months) with identical pCR rate (29% in CROSS) and similar toxicity profile. nCRT with protons should be studied rigorously in the current randomized phase III trial NRG GI006.

Prognostic factors of dose-response relationship for nodal control in metastatic lymph nodes of cervical cancer patients undergoing definitive radiotherapy with concurrent chemotherapy.

ObjectiveRegional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer.MethodsWe identified 115 patients with 417 metastatic nodes who received definitive CRT for cervical cancer with nodal metastases. External beam radiation therapy and brachytherapy plans were summated to determine total dose received by each node. Prognostic factors of nodal control and dose-response relationship were investigated using Cox-regression and restricted cubic spline function.ResultsThe 2-year progression-free survival rate was 69.4%. Among 43 patients with failures, 17 patients (37.5%) had regional failure included in first failure sites of which all except one were in-field only regional failures. Total 30 nodes showed recurrence at initial metastatic site after treatment. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, total radiation dose (minimum dose received by 98% of the target volume in equivalent dose in 2 Gy per fractions), and initial nodal volume ≥5.29 mL were poor prognostic factors (all p<0.050) of nodal local control. Restricted cubic spline functions revealed strongest dose-response relationship in high NLR (NLR ≥3.1) and initial nodal volume ≥5.29 mL subgroup.ConclusionInitial nodal volume, radiation dose, and NLR were significant factors of nodal local control in cervical cancer; a stronger dose-response relationship was seen in bulky nodes with high NLR. Clinicians may consider these factors when determining the RT dose and the need for boost to nodal metastases in cervical cancer.

Randomized Phase 3, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Oral Mucositis Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma

The purpose of this paper is to determine whether prophylactic gabapentin usage in patients undergoing definitive concurrent chemotherapy and radiation therapy (chemoRT) for oropharyngeal cancer (OPC) improves treatment-related oral mucositis pain, opioid use, and feeding tube (FT) placement. This double-blind, randomized phase 3 study for patients with locally advanced OPC undergoing chemoRT randomly allocated patients to prophylactic gabapentin (600 mg thrice daily) or placebo. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores over the entire treatment period (baseline to 6 weeks post-radiation therapy [RT] follow-up) with higher scores indicating worse outcomes. Opioid requirements, FT placement, and other patient-reported quality of life (QOL) metrics (Functional Assessment of Cancer Therapy-Head and Neck [FACT-HN] and Patient-Reported Outcomes version of the National Cancer Institute Common Terminology Criteria for Adverse Events [PRO-CTCAE]) were assessed. Lower scores suggested poorer QOL with the FACT-HN questionnaire, and higher scores suggested worse outcomes with the PRO-CTCAE questionnaire. Questionnaires were administered at baseline, weekly during RT, and at 6 weeks post-RT follow-up. Repeated measures analysis of variance was used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon rank sum tests were used to compare averages for the other secondary endpoints. A P value less than .05 was considered statistically significant. Treatment arms were well balanced overall, including T and N staging and dosimetric variables. There were 58 patients analyzed. No significant difference was found in PROMS scores (mean 29.1, standard deviation [SD] 22.5 vs 20.1, SD 16.8 for gabapentin vs placebo, respectively, P=.11). The FACT-HN functional well-being index had a significant decrease in scores from baseline to follow-up in the gabapentin arm (median -6, interquartile range [IQR] -10.0 to -0.5 vs -1, IQR -5.5 to 3.0, P=.03). PRO-CTCAE scores increased significantly at follow-up for gabapentin (median 6.5, IQR 3.5-11.8 vs 1, IQR -2.0 to 6.0, P=.01). There was no significant difference in average or change in opioid use. FT placement was significantly higher in the gabapentin arm (62.1% vs 20.7%, P < .01). This study suggests that prophylactic gabapentin is not effective in improving treatment-related oral mucositis symptoms in a select population of patients with OPC undergoing definitive chemoRT.

Factors Associated With Treatment Discontinuation in Patients With Muscle-Invasive Bladder Cancer Undergoing Chemoradiation

Radiation treatment with concurrent chemotherapy (CRT) is a definitive treatment option for muscle-invasive bladder cancer (MIBC). Despite its effectiveness, CRT is underutilized given perceptions regarding fitness of patients for treatment and subsequent utility. Within the national Veterans Affairs' (VA) database, we investigated the factors associated with and the impact of treatment discontinuation in patients with MIBC treated with CRT.In the VA database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 and 2018 and treated with definitive intent CRT. Patients' electronic health records were chart reviewed to document if they completed definitive radiation (defined as at least 55 Gy). Preferred chemotherapy regimen was defined as containing cisplatin or combination mitomycin/5-fluorouracil. Primary endpoint of discontinued radiation was evaluated in a multivariable logistic regression. Secondary endpoints of 30/90-day mortality, overall mortality (OM), bladder cancer-specific mortality (BCM), non-bladder cancer-specific mortality (NCM), locoregional failure (LRF), and distant failure (DF) were evaluated in multivariable Cox and Fine-Gray models.Of an identified 369 veterans with MIBC who underwent CRT, 30 (8.1%) patients did not complete definitive radiation. The most common reasons for treatment discontinuation included comorbidities/infections necessitating hospital admission (63.3%) and treatment intolerance/declining performance status (26.7%). In multivariable logistic regression, the only significant sociodemographic or clinical variables associated with radiation discontinuation were creatinine clearance (CrCl) ≤ 50 (OR 3.61, 95% CI 1.51-8.66, P < 0.01) and non-preferred chemotherapy regimen (OR 3.43, 95% CI 1.36-8.67, P = 0.01). In the discontinued radiation cohort, 30-day mortality was 33.3% and 90-day mortality was 50.0% with the majority of deaths due to non-bladder cancer-specific causes. In this cohort, no patient or tumor variables were associated with either endpoint. In the completed radiation cohort, 30-day mortality was 2.7% and 90-day mortality was 6.8%. In multivariable analysis, radiation discontinuation was significantly associated with worse OM (HR 2.50, 95% CI 1.37-4.56, P < 0.01) and worse NCM (HR 2.29, 95% CI 1.21-4.32, P = 0.01). It was not associated with inferior BCM (HR 0.56, 95% CI 0.25-1.26, P = 0.16), LRF (HR 0.93, 95% CI 0.44-1.97, P = 0.85), or DF (HR 0.60, 95% CI 0.28-1.28, P = 0.19).More than 90% of patients with MIBC who undergo definitive intent CRT are able to complete their radiation course. Decreased creatinine clearance and receipt of non-preferred chemotherapy notably increased the odds of not completing radiation. Further research is required to develop evidence-based guidelines on patient selection to ensure curative therapy is offered to appropriate patients.

Esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal squamous cell carcinoma.

BackgroundThe literature regarding esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal squamous cell carcinoma (ESCC) remains lacking. We aimed to investigate the risk factors of esophageal fistula among ESCC patients undergoing definitive concurrent chemoradiotherapy (CCRT) via IMRT technique.MethodsA total of 129 consecutive ESCC patients receiving definitive CCRT with IMRT between 2008 and 2018 were reviewed. The cumulative incidence of esophageal fistula and survival of patients were estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The risk factors of esophageal fistula were determined with multivariate Cox proportional hazards regression analysis.ResultsMedian follow-up was 14.9 months (IQR, 7.0–28.8). Esophageal perforation was identified in 20 (15.5%) patients, resulting in esophago-pleural fistula in nine, esophago-tracheal fistula in seven, broncho-esophageal fistula in two, and aorto-esophageal fistula in two patients. The median interval from IMRT to the occurrence of esophageal fistula was 4.4 months (IQR, 3.3–10.1). Patients with esophageal fistula had an inferior median overall survival (10.0 vs. 17.2 months, p = 0.0096). T4 (HR, 3.776; 95% CI, 1.383–10.308; p = 0.010) and esophageal stenosis (HR, 2.601; 95% CI, 1.053–6.428; p = 0.038) at baseline were the independent risk factors for esophageal fistula. The cumulative incidence of esophageal fistula was higher in patients with T4 (p = 0.018) and pre-treatment esophageal stenosis (p = 0.045). There was a trend toward better survival after esophageal fistula among patients receiving repair or stenting for the fistula than those only undergoing conservative treatments (median survival, 5.9 vs. 0.9 months, p = 0.058).ConclusionsT4 and esophageal stenosis at baseline independently increased the risk of esophageal fistula in ESCC treated by definitive CCRT with IMRT. There existed a trend toward improved survival after the fistula among patients receiving repair or stenting for esophageal perforation.

Cardiac radiation dose predicts survival in esophageal squamous cell carcinoma treated by definitive concurrent chemotherapy and intensity modulated radiotherapy

BackgroundThe prognostic significance of cardiac radiation dose in esophageal cancer after definitive concurrent chemoradiotherapy (CCRT) remains largely unknown. We aimed to investigate the association between cardiac dose-volume parameters and overall survival (OS) in esophageal squamous cell carcinoma (ESCC) after definitive CCRT.MethodsOne hundred and twenty-one ESCC patients undergoing definitive CCRT with intensity modulated radiotherapy technique between 2008 and 2018 were reviewed. Cardiac dose-volume parameters were calculated. Survival of patients and cumulative incidence of adverse events were estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The prognostic significance of cardiac dose-volume parameters was determined with multivariate Cox proportional hazards regression analysis.ResultsMedian follow-up was 16.2 months (range, 4.3–109.3). Median OS was 18.4 months. Heart V5, V10, and V20 were independent prognostic factors of OS. Median OS was longer for patients with heart V5 ≤ 94.3% (24.7 vs. 16.3 months, p = 0.0025), heart V10 ≤ 86.4% (24.8 vs. 16.9 months, p = 0.0041), and heart V20 ≤ 76.9% (20.0 vs. 17.2 months, p = 0.047). Lower cumulative incidence of symptomatic cardiac adverse events was observed among patients with heart V5 ≤ 94.3% (p = 0.017), heart V10 ≤ 86.4% (p = 0.02), and heart V20 ≤ 76.9% (p = 0.0057). Patients without symptomatic cardiac adverse events had a higher 3-year OS rate (33.8% vs. 0%, p = 0.03).ConclusionsCardiac radiation dose inversely correlated with survival in ESCC after definitive CCRT. Radiation dose to the heart should be minimized.

Pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal cancer

BackgroundThe literature regarding pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal cancer was lacking. This study aimed to investigate the risk factors of pericardial effusion in esophageal cancer patients undergoing definitive concurrent chemotherapy and IMRT.MethodsA total of 126 consecutive esophageal cancer patients treated with definitive concurrent chemotherapy and IMRT between 2008 and 2018 were reviewed. The pericardial effusion was determined on computed tomography scan of the chest and graded by the Common Terminology Criteria for Adverse Events, version 4.0. The cumulative incidence of pericardial effusion was estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The risk factors of pericardial effusion were determined with multivariate Cox proportional hazards regression analysis.ResultsThe median follow-up time was 14.0 months. Thirty-seven (29.4%) patients had pericardial effusion after a median interval of 6.6 months since the end of IMRT. The cumulative incidence of pericardial effusion of any grade was higher in patients with mean heart dose > 23.45 Gy (p = 0.00018), heart V30 > 33.55% (p = 0.00015), mean pericardium dose > 20.33 Gy (p = 0.00027), and pericardium V20 > 42.55% (p = 0.00018). Furthermore, eight (6.3%) patients had symptoms related to pericardial effusion and were considered as cases with pericardial effusion ≥ grade 3. The cumulative incidence of pericardial effusion ≥ grade 3 was higher in patients with pericardium V30 > 65.80% (p = 0.00028), V40 > 55.35% (p < 0.0001), and V60 > 24.70% (p = 0.0021). Multivariate analyses showed the above dose-volume parameters predicted the risk of pericardial effusion in esophageal cancer.ConclusionsDose-volume parameters predicting the risk of pericardial effusion were identified in esophageal cancer treated with definitive concurrent chemotherapy and IMRT. They could be applied as constraints of IMRT for esophageal cancer.

Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives.

There has been no improvement in outcome for patients with unresectable locally advanced (stage III) non–small cell lung cancer (NSCLC) for more than 10 years. The standard treatment for these patients is definitive concurrent chemotherapy and radiation (CCRT). Although the goal of treatment in this setting is to achieve a cure, most patients progress and their prognosis is poor, with a 5-year survival rate of 15–30%. There is thus an urgent need for the development of novel anticancer treatments in this patient population. Recent advances in cancer immunotherapy have led to a marked improvement in clinical outcome for advanced NSCLC. Such immunotherapy mainly consists of the administration of immune checkpoint inhibitors (ICIs) such as antibodies to cytotoxic T lymphocyte–associated protein–4 (CTLA-4) or to either programmed cell death–1 (PD-1) or its ligand PD-L1. Durvalumab (MEDI4736) is a high-affinity human immunoglobulin G1 monoclonal antibody that blocks the binding of PD-L1 on tumor cells or antigen-presenting cells to PD-1 on T cells. The PACIFIC study recently evaluated consolidation immunotherapy with durvalumab versus placebo administered after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage III NSCLC. It revealed a significant improvement in both progression-free and overall survival with durvalumab, and this improvement was associated with a favorable safety profile. This achievement has made durvalumab a standard of care for consolidation after CCRT in patients with unresectable stage III NSCLC, and it has now been approved in this setting by regulatory agencies in the United States, Canada, Japan, Australia, Switzerland, Malaysia, Singapore, India, and the United Arab Emirates. In this review, we briefly summarize the results of the PACIFIC trial, including those of post hoc analysis, and we address possible molecular mechanisms, perspectives, and remaining questions related to combined treatment with CCRT and ICIs in this patient population.

Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer

For more than a decade, there has been no improvement in outcomes for patients with unresectable locally advanced (la) non-small-cell lung cancer (nsclc). The standard treatment in that setting is definitive concurrent chemotherapy and radiation (ccrt). Although the intent of treatment is curative, most patients rapidly progress, and their prognosis is poor, with a 5-year overall survival (os) rate in the 15%–25% range. Those patients therefore represent a critical unmet need, warranting expedited approval of, and access to, new treatments that can improve outcomes. The pacific trial, which evaluated durvalumab consolidation therapy after ccrt in unresectable la nsclc, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (pfs) and a significant improvement in os. Durvalumab thus fills a critical unmet need in the setting of unresectable la nsclc and provides a new option for patients treated with curative intent. Here, we review the treatment of unresectable la nsclc, with a focus on the effect of the clinical data for durvalumab.

Comparative analysis between induction chemotherapy combined with concurrent chemoradiotherapy and chemoradiotherapy alone for thoracic esophageal squamous cell carcinoma

Objective To compare the clinical efficacy and safety between induction chemotherapy (IC) followed by concurrent chemotherapy (CRT) and CRT alone in patients with inoperable thoracic esophageal squamous cell carcinoma (ESCC). Methods Between 2002 and 2015, clinical data of 267 thoracic ESCC patients undergoing definitive CRT based on docetaxel combined with cisplatin were retrospectively analyzed. Through a matched case-control study, 85 patients receiving IC combined with CRT were matched to those undergoing CRT alone at a ratio of 1vs.1, according to age, gender, performance status, tumor location, tumor length, and TNM staging as the matching factors. Clinical efficacy and safety between two groups were statistically compared. Kaplan-Meier survival analysis was used to analyze the survival. The log-rank test was adopted to examine within-group differences. The Cox regression model was used for multivariate analysis. Results The median follow-up time for 170 patients was 18 months (range, 3-72 months). The overall objective response rates in the IC and CRT groups were 74.1% and 58.8%(P=0.035). The 3-year overall survival (OS) and progress-free survival (PFS) rates in the IC group were 44.2% and 34.8%, significantly higher than 29.7% and 15.4% in the CRT group (P=0.028, P=0.015). Subgroup analysis revealed that patients responsive to IC obtained significantly better OS (P=0.002), PFS (P=0.001), and local recurrence-free survival (LRFS)(P=0.002) compared with the IC non-responder, whereas the distant metastasis-free survival (DMFS) did not significantly differ (P=0.166). The incidence rate of grade 3–4 leukopenia in the IC group was significantly higher than that in the CRT group (38.8% vs. 24.7%, P=0.048). Multivariate analysis revealed that age and the addition of IC were independent prognostic factors for OS (P=0.003, 0.016). Conclusions Compared with concurrent CRT, IC in combination with CRT can yield better short-term efficacy and longer survival for ESCC patients. The risk of hematological toxicity in the IC group is relatively higher but tolerable. Prospective randomized trials are required to confirm the clinical efficacy and safety of IC for thoracic ESCC patients. Key words: Esophageal neoplasms/concurrent chemoradiotherapy; Induction chemotherapy; Prognosis

Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer.

For more than a decade, there has been no improvement in outcomes for patients with unresectable locally advanced (la) non-small-cell lung cancer (nsclc). The standard treatment in that setting is definitive concurrent chemotherapy and radiation (ccrt). Although the intent of treatment is curative, most patients rapidly progress, and their prognosis is poor, with a 5-year overall survival (os) rate in the 15%-25% range. Those patients therefore represent a critical unmet need, warranting expedited approval of, and access to, new treatments that can improve outcomes. The pacific trial, which evaluated durvalumab consolidation therapy after ccrt in unresectable la nsclc, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (pfs) and a significant improvement in os. Durvalumab thus fills a critical unmet need in the setting of unresectable la nsclc and provides a new option for patients treated with curative intent. Here, we review the treatment of unresectable la nsclc, with a focus on the effect of the clinical data for durvalumab.

The Radiosensitivity of Cervical Cancer and its Influence on Patterns of Failure Following Definitive Concurrent Chemotherapy and Radiation

The Radiosensitivity of Cervical Cancer and its Influence on Patterns of Failure Following Definitive Concurrent Chemotherapy and Radiation

Organ preservation for advanced larynx cancer: A review of chemotherapy and radiation combination strategies

The larynx is an organ of the upper aerodigestive tract that is involved in many critical functions such as breathing, speaking, and swallowing. As a result, both larynx cancer and its treatment may significantly affect quality of life. The management of laryngeal cancer has focused on improving survival while preserving the function of the organ. This manuscript focuses on the use of chemotherapy and radiation therapy as a non-surgical approach and potential organ preservation strategy for patients with advanced larynx cancer. We review the key clinical data on the following treatment courses: (1) induction chemotherapy followed by definitive radiation therapy, (2) concurrent chemotherapy and radiation, and (3) induction chemotherapy followed by concurrent chemo-radiation. We also review the clinical data on organ preservation for patients with hypopharynx cancers. Results from phase III studies suggest that patients with advanced T4 cancers have better outcomes with a primary surgical approach, while for patients with T2N+ and T3 tumors, definitive concurrent chemotherapy and radiation or induction chemotherapy followed by definitive radiation therapy are acceptable options. Choosing the optimal treatment strategy depends on patients’ desires, tumor extent, and adequate follow-up to detect early recurrences in cases of larynx preservation treatments. To proceed with an organ preservation strategy, the patient should have a good pre-treatment larynx function, and there must be a high level of skill and cooperation among various disciplines.

Treatment outcomes and HPV characteristics for an institutional cohort of patients with anal cancer receiving concurrent chemotherapy and intensity-modulated radiation therapy.

BackgroundIntensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported.Materials and methods52 patients with anal SCC were treated with IMRT and concurrent chemotherapy. Radiation was delivered sequentially to the pelvis and inguinal lymph nodes (45 Gy) and anal tumor (median dose, 54 Gy). Multiplex real-time PCR for 7 high-risk HPV subtypes (n = 22) and p16 immunohistochemistry (n = 21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and toxicities were recorded.ResultsMedian follow-up was 33 months. Three-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 90%, respectively. Acute grade 2+ skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. The rates of late grade 2+ GI and GU toxicities for evaluable patients (n = 32) were 28% and 9%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (n = 17), 33 (n = 2), 18 (n = 1), and 45 (n = 1). HPV and p16 status were associated on Chi-square analysis (p = 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 3-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 88%, respectively.ConclusionsIn this patient cohort, disease control was excellent for anal SCC treated with definitive concurrent chemotherapy and IMRT, and treatment was well tolerated. HPV and p16 status were not prognostic for treatment outcomes which may be related to our small sample size.

Comprehensive analyses of the clinical benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer.

168 Background: Treatment with immune checkpoint inhibitors is becoming the standard of care for patients and it was approved for the treatment of non-small-cell lung cancer (NSCLC) growing at a rapid pace. However, selecting patients who are appropriate for therapy and which therapeutic strategies to use can be challenging. Methods: We searched for randomized clinical trials (RCTs) investigating immune checkpoint inhibitors versus observation in patients with advanced NSCLC until September 2017. Overall survival (OS) and progression-free survival (PFS) were pooled by meta-analysis. The GRADE system was used to describe the quality of evidence. Results: The analysis included 11 trials with 5,538 unique patients. High- to moderate-quality evidence indicated that immune checkpoint inhibitors extended NSCLC survival and PFS, expressed as hazard ratios (HRs) (OS: 0.79, P = 0.000; PFS: 0.78, P = 0.000). High- to moderate-quality evidence revealed prolonged OS and PFS were similar across preplanned subgroups in patients with squamous (0.77, P = 0.000 and 0.74, P = 0.001) or nonsquamous disease (0.76, P = 0.003 and 0.73, P = 0.041), EGFR wild-type positive status (0.67, P = 0.000 and 0.59, P = 0.010), current or former smokers (OS: 0.83, P = 0.009), and male (0.79, P = 0.000 and 0.67, P = 0.023). Increasing improvement in OS was associated with increasing PD-L1 expression (TC3 or IC3 HR 0.54, P = 0.000; TC2/3 or IC2/3 HR 0.62, P = 0.007; TC1/2/3 or IC1/2/3 HR 0.64, P = 0.000; TC0 and IC0 HR 0.72, P = 0.017; high- to moderate-quality evidence). In exploratory subgroup analysis suggest that there was advantageous of immune checkpoint inhibitors in previous definitive chemotherapy compared with chemoradiotherapy, with concurrent administration of chemotherapy (OS as HR: P = 0.001, P = 0.006, respectively). Conclusions: This large and comprehensive analysis produced firm evidence that immune checkpoint inhibitors extended advanced NSCLC survival and PFS, while in some patients with EGFR wild-type positive status, current or former smokers, male and higher PD-L1 expression had substantial benefit. The benefits from therapy appear to be influenced by preceding definitive therapy and concurrent chemotherapy.

Anorectal function and quality of life after chemoradiotherapy in patients with anal canal carcinoma

Background: A retrospective study was conducted to evaluate sphincter function and quality of life (QoL) in patients treated with radiotherapy and concurrent chemotherapy (CRT) for anal canal cancer.&#x0D; Materials and Methods: From 1998 to 2010, patients with anal canal cancer treated with CRT were eligible. Radiation dose was 59.4 Gy (1.8 Gy/ fraction) and the chemotherapy regimen was 5-fluorouracil and mitomycin C. Anorectal function was investigated by anorectal manometry and transrectal ultrasound. QoL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C29 questionnaire. Correlations between diagnostic parameters and patient-reported outcomes were evaluated.&#x0D; Results: Eighteen patients were enrolled. Overall, 4 patients had stage I disease, 8 stage II and 6 stage III. Anorectal manometry parameters were significantly lower compared to healthy scores. Patients-reported continence was significantly higher than fecal incontinence manometry scores. Ultrasound sphincter complex defects were recorded in 17 patients. Globally, a positive correlation was described between resting pressure of manometric exam and sexual functioning items and sphincter complex and patient-reported flatulence, respectively.&#x0D; Conclusions: Definitive CRT represents the standard of care for anal canal cancer. Patients experienced low rates of fecal incontinence compared with results of diagnostic exams. Further studies are needed to better define toxicity and QoL after definitive CRT in anal canal cancer.

Radiation Treatment Time and Overall Survival in Locally Advanced Non-small Cell Lung Cancer

Prolonged radiation treatment (RT) time (RTT) has been associated with worse survival in several malignancies. The present study investigated whether delays during RT are associated with overall survival (OS) in non-small cell lung cancer (NSCLC). The National Cancer Database was queried for patients with stage III NSCLC who had received definitive concurrent chemotherapy and fractionated RT to standard doses (59.4-70.0Gy) and fractionation from 2004 to 2013. The RTT was classified as standard or prolonged for each treatment regimen according to the radiation dose and number of fractions. Cox proportional hazards models were used to evaluate the association between the following factors and OS: RTT, RT fractionation, demographic and pathologic factors, and chemotherapeutic agents. Of 14,154 patients, the RTT was prolonged in 6262 (44.2%). Factors associated with prolonged RTT included female sex (odds ratio [OR] 1.21, P<.0001), black race (OR 1.20, P=.001), nonprivate health insurance (OR 1.30, P<.0001), and lower income (<$63,000 annually, OR 1.20, P<.0001). The median OS was significantly worse for patients with prolonged RTT than that for those with standard RTT (18.6 vs 22.7months, P<.0001). Furthermore, the OS worsened with each cumulative interval of delay (standard RTT vs prolonged 1-2days, 20.5months, P=.009; prolonged 3-5days, 17.9months, P<.0001; prolonged 6-9days, 17.7months, P<.0001; prolonged >9days, 17.1months, P<.0001). On multivariable analysis, prolonged RTT was independently associated with inferior OS (hazard ratio 1.21, P<.0001). Prolonged RTT as a continuous variable was also significantly associated with worse OS (hazard ratio 1.001, P=.0007). Delays during RT appear to negatively affect survival for patients with locally advanced NSCLC. We have detailed the demographic and socioeconomic barriers influencing prolonged RTT as a method to address the health disparities in this regard. Cumulative interruptions of RT should be minimized.

Feasibility study of toxicity outcomes using GEC-ESTRO contouring guidelines on CT based instead of MRI-based planning in locally advanced cervical cancer patients

PurposeTo report late rectal and bladder toxicity outcomes of a CT-based image-guided brachytherapy (IGBT) technique for treatment of cervical cancer. Methods and MaterialsBetween 2008 and 2014, 95 women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma treated with definitive concurrent cisplatin-based chemotherapy and external beam radiation therapy 50.4 Gy in 28 fractions followed by planned prescription dose of 7 Gy × 4 fractions of high-dose-rate IGBT was retrospectively reviewed. At each implantation, all patients had a urinary catheter in situ and received bowel enema before undergoing planning CT simulation. A high-risk clinical target volume (HRCTV) as per GEC-ESTRO guidelines and the entire cervix, rectum, and bladder was contoured on the simulation CT according to Radiation Therapy Oncology Group Gynaecology Contouring Atlas. Reported doses to HRCTV and organs at risk were recorded. Toxicities were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 3. ResultsThe median followup time was 29 months. The mean HRCTV equivalent dose in 2 Gy fractions (EQD2) of external beam radiation therapy combined with brachytherapy was 80 Gy (standard deviation [SD], 11), and the rectal doses to 2 cm3 (D2cc) EQD2 and bladder D2cc EQD2 were 74 Gy (SD, 6) and 79 Gy (SD, 15), respectively. Twenty-two patients (23%) had grade 2 proctitis and 10 patients (11%) had grade 3 proctitis. Four patients (4%) had grade 2 cystitis and two patients (2%) had grade 3 cystitis. No patients had ≥ grade 4 toxicity. ConclusionsDespite CT-based brachytherapy planning, reported organ at risk toxicity was still significant compared with reported MRI-based planning series. Coimplementation of interstitial IGBT using the European Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE) protocol or using intensity-modulated radiation therapy during the external beam phase treatment might help to limit these late toxicities.