Adjuvant Concurrent Chemoradiotherapy Research Articles

Comparison of outcomes between early-stage cervical cancer patients without high-risk factors undergoing adjuvant concurrent chemoradiotherapy and radiotherapy alone after radical surgery.

For patients with early-stagecervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rateswere 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.

Neoadjuvant Chemotherapy Alone or Combined with EGFR-Directed Targeted Therapy or Anti-PD-1 Immunotherapy for Locally Advanced Lacrimal Sac and Nasolacrimal Duct Carcinomas

ABSTRACT Background/aims We describe our findings in patients with locally advanced lacrimal sac and nasolacrimal duct (NLD) carcinoma who received neoadjuvant systemic therapy. Methods We identified patients with locally advanced primary lacrimal sac/NLD carcinoma treated with neoadjuvant systemic intravenous therapy at our institution during 2017–2019. Results The study included seven patients, four men and three women; the mean age was 60.4 years (range: 43–76). All patients had locally advanced disease with significant orbital soft tissue invasion with or without skull base invasion making eye-sparing surgery not feasible as an initial step. Three patients had poorly differentiated squamous cell carcinoma; two, invasive carcinoma with basaloid and squamous features; one, high-grade carcinoma with features suggestive of sebaceous differentiation; and one, undifferentiated carcinoma. The neoadjuvant regimens were cisplatin and docetaxel (n = 1); carboplatin and docetaxel (n = 1); paclitaxel and cetuximab (n = 1); carboplatin, paclitaxel, and cetuximab (EGFR inhibitor) (n = 2); cisplatin, docetaxel, and pembrolizumab (anti-PD-1 immunotherapy) (n = 1); and carboplatin, paclitaxel, and pembrolizumab (n = 1). All patients had radiologic disease regression, and one patient had radiologic near-complete response. After neoadjuvant therapy, all patients underwent wide local excision and adjuvant concurrent chemoradiation. Two patients had a complete pathologic response. At a median follow-up period of 13 months after chemoradiation (range, 8–54 months), all patients were alive without evidence of disease. One patient had nodal metastasis treated with lymph node dissection and adjuvant chemoradiation. Conclusions Neoadjuvant systemic therapy can shrink tumors in patients with locally advanced primary lacrimal sac/NLD carcinoma with orbital or skull base invasion.

Acute Diabetes-Related Complications in Patients Receiving Chemoradiotherapy for Head and Neck Cancer.

Consecutive patients with head and neck squamous cell or nasopharyngeal cancer who underwent definitive or adjuvant CCRT between 2010 and 2019 at two large cancer centers in Australia were included. Clinicopathological characteristics, treatment complications and outcomes were collected from medical records. Of 282 patients who received CCRT, 29 (10.3%) had pre-existing type 2 diabetes. None had type 1 diabetes. The majority (74.5%) required enteral feeding. A higher proportion of patients with diabetes required admission to a high-dependency or intensive care unit (17.2 versus 4.0%, p = 0.003). This difference was driven by the group who required insulin at baseline (n = 5), of which four (80.0%) were admitted to a high-dependency unit with diabetes-related complications, and three (60.0%) required omission of at least one cycle of chemotherapy. Patients with diabetes requiring insulin have a high risk of acute life-threatening diabetes-related complications while receiving CCRT. We recommend multidisciplinary management involving a diabetes specialist, educator, dietitian, and pharmacist, in collaboration with the cancer care team, to better avoid these complications.

Clinical value of magnetic resonance spectroscopy in assessment of early curing impact of concurrent chemoradiotherapy after high-grade glioma surgery

Background/Aim. High-grade glioma (HGG) is an interstitial cell-derived primary tumor of the nervous system. The current guidelines for the diagnosis and treatment of glioma recommend the maximum safe range of tumor resection for treatment methods. Adjuvant concurrent chemoradiotherapy is recommended after surgery, followed by six cycles of single-drug chemotherapy, temozolomide. Evaluation of the early efficacy of concurrent chemoradiotherapy after HGG surgery, especially for patients with a high risk of recurrence, is a crucial step in enhancing the treatment efficiency for patients diagnosed with HGG. In this study, we investigated the clinical utility of magnetic resonance (MR) spectroscopy (MRS) in assessing the early curing impact of concurrent chemoradiotherapy following HGG surgery. Methods. A total of 50 patients with incomplete resection or suspected residual postoperative HGG, treated in the radiotherapy department of our hospital between January 2016 and June 2021, were selected for routine concurrent chemoradiotherapy. Conventional MR imaging and MRS were performed one week prior to treatment and one month after treatment to assess changes in specific brain metabolites. All 50 patients were followed up for 6 to 12 months. Based on the follow-up results, the patients were divided into two groups: the tumor recurrence group and the tumor suppression group. One month after the end of the treatment, the differences in levels of brain metabolites between the two groups were analyzed using MRS. Results. The levels of N-acetylaspartate (NAA) and creatine (Cr) increased after radiotherapy, while choline (Cho) peak value, and Cho/Cr, NAA/Cr, and Cho/NAA ratios decreased compared to pre-treatment levels. There were statistically significant differences in the NAA peak value, and Cho/Cr, and Cho/NAA ratios in the tumor enhancement area before and after treatment (p &lt; 0.05). There were also statistically significant differences in Cho/Cr ratio in the peritumoral edema area before and after treatment (p &lt; 0.05). Conclusion. After concurrent chemoradiotherapy, MRS can be used to detect early metabolic changes in the tumor enhancement and peritumoral edema areas of HGG.

Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: a real-world retrospective study.

The treatment of locally advanced oral or oropharyngeal squamous cell carcinoma (LAOOPSCC) is surgery and radiotherapy or chemoradiotherapy but with unsatisfactory survival rate. Neoadjuvant programmed death-1 (PD-1) therapy are being used in several clinical trials. Therefore, in this retrospective study we aimed to determine the feasibility of neoadjuvant tislelizumab plus chemotherapy followed by surgery for LAOOPSCC. The clinical data of 33 patients with LAOOPSCC who received neoadjuvant PD-1 inhibitors and chemotherapy between April 2021 and October 2022 were retrospectively analyzed. Patients with stage III-IV LAOOPSCC received tislelizumab, albumin-bound paclitaxel, and cisplatin every 3 weeks (Q3W) for two cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. A median follow-up period was 20 months. The objective response rate (ORR) was 66.7%, with the major pathological response (MPR) rate at 54.5%, and the pathological complete response (pCR) rate was 33.3%. Sixteen patients underwent limited surgeries, and 15 patients were remitted from undergoing mandibulectomy and 9 patients were remitted from undergoing near total glossectomy or total glossectomy. A significant difference in the overall survival (OS) and disease-free survival (DFS) was observed in patients who achieved major pathological response (MPR) than who did not. The most common adverse events in neoadjuvant therapy were alopecia, decreased appetite or anorexia, leukopenia, and fatigue. Neoadjuvant PD-1 inhibitors combined with chemotherapy are feasible and safe, with a high pathological response and possible organ preservation in oral or oropharyngeal squamous cell carcinoma. However, further studies with a larger cohort of patients and longer follow-up period is required to strengthen our findings and evaluate the survival benefits of the treatment.

Prospective Evaluation of Locoregional Control in Oral Cavity Squamous Cell Carcinoma with Infratemporal Fossa Involvement Treated with Surgery and Adjuvant Concurrent Chemoradiotherapy

Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck cancer in India. Definitive surgery with or without post-op radiotherapy (PORT) with or without chemotherapy (CT) provides better outcomes in locally advanced OCSCC as compared to definitive chemoradiotherapy. T4b OCSCC with infra temporal fossa (ITF) involvement has varied outcome depending on the extent of ITF involvement, with low and mid ITF having relatively favorable prognosis. We aimed to prospectively evaluate outcomes in patients of OCSCC with low or mid ITF involvement treated with curative surgery followed by adjuvant concurrent chemoradiotherapy (CCRT). A total of 20 patients of T4b OCSCC (as per AJCC 8th edition) with low or mid ITF involvement were included in this single arm prospective interventional study from January 2021 to October 2022. Patients with involvement of skull base, carotid artery, prevertebral fascia and/or pterygomaxillary fissure were excluded. All patients were treated with definitive surgery with ITF clearance followed by adjuvant CCRT as indicated. Loco-regional control (LRC), Disease free survival (DFS), Overall survival (OS) were assessed using Kaplan-Meier survival analysis. Acute toxicities were assessed according to the CTCAE v5.0. Patient characteristics are summarized in table 1. Median follow-up was 11.5 months (4-21months). All patients received adjuvant CCRT with weekly cisplatin 40mg/m2 to a median number of 6 cycles (5-7 cycles). Median RT dose was 64Gy (60-64Gy). All patients tolerated treatment well. Grade 3 oral mucositis, odynophagia were seen in 8 (40%) patients each and skin toxicity, oral pain in 6 (30%) and 5 (25%) patients respectively. No grade 4 toxicities were observed LRC at three month was 73.68% with 4 local and 1 locoregional failure only. LRC at one year was 36.8% with 8 local, 1 locoregional, 2 locodistant and 1 distant failure only. Median DFS was 10.4 months. Median OS was not reached; four patients died. LRC at three months was better for patients with low ITF disease as compared to mid ITF disease (85.7% vs. 40% (p = 0.04) and at one year was 42.8% vs. 40% (p = 0.50). Selected patient of locally advanced OCSCC with low ITF involvement may benefit from trimodality therapy of surgery with ITF clearance followed by adjuvant CCRT. Acute toxicity profile was acceptable in our study.

Adjuvant Concurrent Chemoradiotherapy vs. Radiotherapy Alone in Cervical Cancer Patients with Intermediate-Risk Factors after Radical Surgery

For early-stage cervical cancer patients with intermediate-risk factors, there is no consensus about whether postoperative concurrent chemoradiotherapy (CCRT) is superior to radiotherapy (RT) alone. We retrospectively reviewed medical records of stage I-IIA cervical cancer patients underwent radical surgery and postoperative RT or CCRT from June 2012 to December 2017. Patients with any of the high-risk factors including positive pelvic lymph node, positive resection margin, and parametrial invasion were excluded. Patients with any of the intermediate-risk factors including large tumor size (≥4cm), deep stromal invasion (≥1/2), and lymphovascular space involvement were included. 1:1 propensity score matching was performed to balance baseline variables between patients receiving RT and CCRT. A total of 350 patients were enrolled (84 underwent RT alone and 266 underwent CCRT). The median follow-up period was 50.4 months. For patients underwent RT alone and CCRT, the 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), the 5-year disease-free survival (DFS) rates were 90.6% and 91.4% (p = 0.733), respectively. 83 pairs of patients were enrolled based on propensity score matching. Similarly, there was no significant difference between OS or DFS rates of those matched patients. For patients with single intermediate-risk factor who received RT alone (n = 58) and CCRT (n = 132), the 5-year OS rates were 94.2% and 95.7% (p = 0.636), the 5-year DFS rates were 92.8% and 94.1% (p = 0.637). For patients with multiple intermediate-risk factors who received RT alone (n = 26) and CCRT (n = 134), the 5-year OS rates were 91.8% and 91.7% (p = 0.761), the 5-year DFS rates were 85.4% and 88.4% (p = 0.717). The cox regression analysis also indicated that adjuvant CCRT or RT was not an independent prognostic factor for OS or DFS. Otherwise, patients underwent CCRT seemed to develop a higher proportion of grade 3 or higher acute hematologic toxicities than RT group (45.5% and 14.3%, p<0.001). There was no significant difference in OS and DFS between cervical cancer patients with intermediate-risk factors receiving postoperative CCRT and RT alone. Patients underwent CCRT seemed to develop a higher proportion of severe hematologic toxicities than RT alone. To a certain extent, CCRT is not superior to RT alone for intermediate-risk patients.

Parametric Response Mapping of Co-Registered Ivim MRI and PET to Identify Radioresistant Sub-Volumes in Locally Advanced Cervical Carcinoma Undergoing CCRT

To investigate parametric response mapping (PRM) of co-registered positron emission tomography (PET) and intravoxel incoherent motion (IVIM) MRI in locally advanced cervical carcinoma patients to identify sub-volumes that may predict treatment response to adjuvant concurrent chemoradiation therapy (CCRT). Pre- and on-treatment (∼after four weeks of CCRT) diffusion weighted images (DWIs) MRI and pre-treatment PET were performed on 20 cervical cancer patients (median [range] age: 63 [41 to 85]; FIGO staging: 3 IIB, 1 IIIB, 10 IIIC1, 4 IIIC2, 2 IVA; histology: 11 squamous cell carcinoma, 4 endocervical adenocarcinoma; LN status: 4 negative, 16 positive). IVIM MRI maps were generated by Bayesian fitting of a two-compartment IVIM model to the DWIs to produce three-dimensional diffusion coefficient (D) and perfusion fraction (f). Three-dimensional IVIM D and f maps were co-registered to PET standardized uptake value (SUV) maps. Population means of PET SUV, IVIM D and f from pre-treatment scans were calculated to generate thresholds to identify low versus high metabolic (μSUV) regions, low versus high diffused (μD) regions as well as low versus high perfused (μf) regions, respectively. PRM maps were generated using voxel-wise joint histogram analysis to classify voxels within the tumor as highly metabolic and with low cellular density (SUV↑D↑), highly metabolic and with high cellular density (SUV↑D↓), metabolically inactive and with high cellular density (SUV↓D↓), or metabolically inactive and with low cellular density (SUV↓D↑) tissue based on the population mean thresholds. Similar PRM maps were generated using the joint histogram analysis with SUV and f. Summary statistics for these and other imaging parameters were calculated pre- and on-treatment. Univariate analysis was performed to determine relationships between relative change in gross tumor volume (ΔGTV) and pre-treatment imaging measurements. In tumors, on- versus pre-treatment tumor volume (p<.001) significantly decreased, while IVIM f (p = .002) and D (p = .03) significantly increased. Pre-treatment tumor volume (r = .45, p = .04) and PRM SUV↑D↓ (r = .65, p = .002) regions were positively related with ΔGTV, while pre-treatment IVIM D (r = -.64, p = .002), PRM SUV↓f↑ (r = -.52, p = .02) and PRM SUV↓D↑ (r = -.74, p<.001) regions were negatively related with ΔGTV. The latter PRM result suggests that larger regions of low cellular density (as represented by elevated D) + low metabolism result in a reduced change in tumor volume on-treatment, potentially representing a radioresistant sub-volume. PRM, generated from PET and IVIM MRI, was applied to patients with locally advanced cervical carcinoma and radioresistant sub-volumes were identified which may predict treatment response. The complementary information provided from PET and IVIM, combined using PRM, may assist in decision-making to individualize therapies, such as with image guided brachytherapy, to improve patient outcomes.

Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Adjuvant chemotherapy in nasopharyngeal carcinoma

The value of adjuvant chemotherapy after definitive radiotherapy in locoregionally advanced nasopharyngeal carcinoma has been debated since the landmark publication of the Intergroup-0099 trial. 1 Al-Sarraf M LeBlanc M Giri PG et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998; 16: 1310-1317 Crossref PubMed Google Scholar The differing views occur for two reasons: (1) early chemoradiotherapy trials in the 2000s investigated various platinum-based regimens of concurrent chemoradiotherapy alone or in combination with adjuvant chemotherapy, with both strategies showing survival benefits over radiotherapy alone; and (2) it was generally observed that platinum doublet adjuvant chemotherapy after concurrent chemoradiotherapy was poorly tolerated. 2 Chua MLK Wee JTS Hui EP Chan ATC Nasopharyngeal carcinoma. Lancet. 2016; 387: 1012-1024 Summary Full Text Full Text PDF PubMed Scopus (934) Google Scholar The resistance towards recommending adjuvant chemotherapy to patients in the clinic was compounded after a phase 3 trial in China showed that adjuvant cisplatin–fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma compared with concurrent chemoradiotherapy alone. 3 Chen L Hu CS Chen XZ et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012; 13: 163-171 Summary Full Text Full Text PDF PubMed Scopus (432) Google Scholar Concurrent chemoradiotherapy followed by adjuvant cisplatin–gemcitabine versus cisplatin–fluorouracil chemotherapy for N2–3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trialOur findings suggest that concurrent adjuvant cisplatin–gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2–3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. Full-Text PDF

Impact of pre-treatment anemia on survival in locally advanced head neck squamous cell carcinomas treated with radiation with or without concurrent chemotherapy.

e18079 Background: Locally advanced head neck squamous cell carcinomas (LAHNSCCs) are treated either with surgery followed by radiation (RT) alone, surgery followed by concurrent chemoradiation (CTRT) or definitive CTRT. Patients receiving RT need to have an optimal hemoglobin (Hb) level, however there is limited data on what is an optimal pre-treatment Hb level required during RT/CTRT in these patients. Hence we performed this analysis. Methods: This data is a pooled analysis of 3 major randomized studies (RCT) performed in the field of chemoradiation over the last decade. These include, a RCT comparing weekly versus (vs) 3 weekly cisplatin in LAHNSCC‘s, weekly cisplatin vs weekly cisplatin plus nimotuzumab in the definitive setting in LAHNSCC‘s and in cisplatin ineligible patients, a comparison of radiation vs docetaxel plus radiation. The baseline demographics, Hb levels, and outcomes were collected and used for analysis. To ensure unanimity, anemia was defined as &lt; 12g/dL in both males and females. Univariate (UVA) and multivariate analysis (MVA) evaluated the factors affecting anemia. The impact of anemia on locoregional control (LRC), disease free survival (DFS) and overall survival (OS) was studied. Kaplan meier analysis was used for estimation of time to event parameters and log rank test was used for comparison. Cox proportional hazards model was used to test the importance of anemia in presence of other important parameters like age, gender, T and N stage, concurrent chemotherapy including its pattern (weekly vs 3 weekly) and site of disease. Results: We studied 1192 patients. Anemia of any grade was seen in 417 patients (35.0%), with the median Hb levels of the entire cohort being 12.8g/dL (IQR 11.6-13.9). Grade 3 or higher anemia (Hb &lt; / = 8g/dL) was seen in only 2 patients (0.2%). Female gender, oral cavity disease, patients with stage IV disease and those receiving adjuvant CTRT significantly impacted anaemia on UVA (p = 0.000 for all). MVA confirmed advancing age (p = 0.001), female gender (p = 0.000), patients with stage III and IV disease (p = 0.009) and those treated with adjuvant CTRT (p = 0.011) to significantly impact anemia. The LRC in patients with or without anaemia was 12.9 months (95%CI 7.8-18.0) and 23.5 months (95%CI 17.8-29.2) respectively (p = 0.000). Similarly the DFS and OS in anemic and non anemic patients were 9.6months (95%CI 6.0-13.2) vs 18.5months (95%CI 12.4-24.7, p = 0.022) and 21.5months (95%CI 16.3-26.8) vs 39.9months (95%CI 31.0-48.9, p = 0.000) respectively. Conclusions: Pre-treatment anemia in LAHNSCC‘s leads to a decrement in treatment outcomes (LRC, DFS and OS) and is an independent prognostic factor.

Adjuvant capecitabine in advanced nasopharyngeal carcinoma following concurrent chemoradiotherapy: A meta-analysis and systematic review.

e18067 Background: Nasopharyngeal cancer (NPCA)is commonly diagnosed at an advanced stage with a high propensity for distant metastasis to the bone, liver, and lungs. Despite current treatment options, prognosis remains dismal for locally advanced disease with 5-year overall survival (OS) rates between 53 to 80% and 28 to 61% in stages III and IV, respectively. Locally advanced NPCA is commonly treated with induction or adjuvant chemotherapy and concurrent chemoradiotherapy. The survival benefit of cisplatin with 5-flurouracil used after concurrent chemoradiotherapy remains controversial. Some patients are also unable to tolerate the side effects of the chemotherapy doublet after local treatment. Thus, other options which may confer survival advantage are needed. Capecitabine has been investigated in two randomized controlled trials as an adjuvant treatment option after concurrent chemoradiotherapy in locally advanced NPCA with conflicting survival results. This systematic review and meta-analysis sought to examine the effect of adjuvant capecitabine after concurrent chemoradiotherapy in locally advanced NPCA compared with observation on survival outcomes. Methods: A comprehensive systematic search was conducted to examine the effect of adjuvant capecitabine after concurrent chemoradiotherapy in locally advanced NPCA. Systematic search was done using MEDLINE, CENTRAL, Clinicaltrials.gov, and Google Scholar for randomized controlled trials published from inception February 1, 2023. Data on failure-free survival (FFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and adverse events were extracted. Hazard ratios (HR) or relative risks (RR) with 95% confidence intervals (95% CI) were pooled from the included studies and summarized using RevMan 5.3. Results: Two randomized controlled trials (n = 586) with low risk of bias were included in the analysis. The use of adjuvant capecitabine improved FFS (HR 0.51; 95% CI 0.36, 0.73), LRFS (HR 0.42; 95% CI 0.23, 0.74), DMFS (HR 0.58; 95% CI 0.38, 0.89), and OS (HR 0.51, 95% CI 0.31, 0.86). There were more grade 3 to 4 hand-foot syndrome on the capecitabine arm (RR 21.93; 95% CI 2.97, 161.89). There was no significant difference on the incidence of any grade 3 to 4 adverse events, and grades 3 to 4 leukopenia, neutropenia, nausea, and fatigue. There was no significant interstudy heterogeneity observed for all outcomes except for the occurrence of any grade 3 to 4 adverse events (I2 89%). Conclusions: The pooled results show a survival advantage on the use of adjuvant capecitabine after concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma with a tolerable safety profile. Capecitabine may be considered as an adjuvant treatment option for NPCA patients especially those unable to tolerate platinum-based therapy.

Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: A single-arm, phase II trial.

e18072 Background: Previous studies confirmed locally advanced oral or oropharyngeal squamous cell carcinoma (LA OSCC or OPSCC) patients (pts) with a pathological response had higher probability of survival in neoadjuvant settings. Several ongoing trials of neoadjuvant immunotherapy in head and neck cancer showed promising results. However, the optimal regimen remains unclear. This trial aimed to evaluate the efficacy and safety of neoadjuvant therapy with anti-programmed cell death 1 (PD-1) mAb tislelizumab and chemotherapy, followed by surgery and adjuvant radiotherapy/chemoradiotherapy in LA OSCC or OPSCC. Methods: In this phase II, single-arm study, eligible pts aged 18-80 diagnosed with stage III-IV (AJCC v8) resectable or potentially resectable LA OSCC or OPSCC received neoadjuvant therapy with tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m2), and cisplatin (60-75 mg/m2) Q3W for 2 cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. The primary endpoint was major pathologic response (MPR). Secondary endpoints included pathological complete response (pCR), objective response rate (ORR), event-free survival (EFS), overall survival (OS) and safety. Results: Thirty-one pts were enrolled from Mar 2022 to Nov 2022, and completed neoadjuvant therapy, with an ORR of 61.3% (19/31) and CR rate of 6.5% (2/31). Of the 31 pts, 29 pts (18 OSCC, 13 OPSCC) successfully underwent surgery with a median age of 57 (34-72) yrs, smoking history 75.9%, alcohol history 72.4% and 82.8% of male. The clinical stage III, IVA and IVB accounted for 24.1%, 48.3% and 27.6%, respectively. The MPR rate was 65.5% (19/29), of which the pCR rate was 41.4% (12/29). R0 resection rate reached 100%. For the per-protocol population, 58.6% pts (17/29) complaint of symptoms included pain, trismus, dysphagic, and speech disorders, all of them reached remission after 2 cycles of neoadjuvant therapy. No delay of surgery occurred. Grade 3-4 adverse events (AEs) occurred in 3 pts including 3.4% G3 leukopenia, 6.9% G3 anemia and 3.4% G4 thrombocytopenia and mostly chemotherapy related. Grade 1-2 AEs included 13.8% anemia, 3.4% thrombocytopenia, 17.2% leukopenia, 13.8% increased aminotransferase, 3.4% increased creatinine, 3.4% hyperglycemia, 27.6% anorexia, 3.4% vomiting, 3.4% diarrhea, 10.3% constipation, 6.9% rash, 100% alopecia and 17.2% fatigue. Conclusions: Neoadjuvant tislelizumab combined with chemotherapy yielded promising MPR and pCR rates with an acceptable safety profile in LA OSCC or OPSCC. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200056354 .

Adjuvant Therapy in Early-Stage Cervical Cancer Patients with Intermediate-Risk Factors, Comparing Between Chemotherapy and Radiotherapy: A Systematic Review and Meta-Analysis

BACKGROUND: Patients with early-stage cervical cancer (ESCC) after radical hysterectomy surgery usually need additional adjuvant treatment, but it depends on the presence or absence of certain risk factors. Factors, such as large tumor size, deep stromal invasion, and lymphovascular space involvement, are classified as intermediate risks. Therefore, postoperative adjuvant concurrent chemo-radiotherapy (CRT) or radiotherapy (RT) is recommended for ESCC with risk factors. However, it remains controversial whether CRT is superior to RT as an adjuvant regimen for postoperative with risk factors. METHODS: A systematic search was performed within PubMed, Cochrane, Science Direct, and Google Scholar databases to research the outcome between CRT and RT in ESCC. Three reviewers independently reviewed titles, abstracts, and full article text to identify studies meeting inclusion and exclusion criteria. If there are any discrepancies, it will be resolved by discussion. In this analysis, the Newcastle–Ottawa scale was used to assess the risk of bias of non-randomized studies. We used review manager 5.4 to calculate the result of 95% CI for the outcomes using odds ratio (OR), random effect model was also used if there is heterogeneity. The primary endpoints of interest are recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 14 studies included in qualitative synthesis and meta-analysis with a total of 5.294 patients were identified. Patients who had RT after radical hysterectomy was found to significantly have a more favorable RFS rate with OR 0.57 95% CI (0.38–0.84), p = 0.005; I2 = 63%. Nine studies were found comparing the OS between adjuvant RT and adjuvant CRT in a patient with ESCC with intermediate risk, the result is quite similar favoring adjuvant RT with significantly better OS outcome OR 0.69 95% CI (0.54–0.87), p = 0.002; I2 =34%. 1.526 had hematologic toxicities, 797 were RT and 729 had CRT. The study showed RT had better outcomes with lesser toxicities (OR 0.11, 95% CI [0.03–0.44] p = 0.002; I2 = 91%). Non-hematological toxicity, with a total of 1.463 patients, 799 were RT and 664 had CRT. Random models were used due to heterogeneity. RT is significantly associated with lesser non- hematologic toxicities with OR 0.34, 95% CI (0.18–0.66) p = 0.001; I2 = 65%. DISCUSSION: During the last two decades, there were significant changes in practice to cure uterine cervical cancer. Based on the consistent results generated in several previous randomized controlled trials, cisplatin-based CCRT has become the standard treatment for advanced cervical cancer. A randomized prospective studies by Sedlis et al., randomized FIGO IB patients without residual tumor or involved lymph nodes but with two or more intermediate-risk factors later named the “Sedlis criteria” to receive observation or RT following radical surgery. Adjuvant RT led to a reduction of recurrence rates at the cost of an approximately 4% higher rate of grade 3/4 adverse events. There was no increase in OS but an improvement of long-term RFS. On the other hand, a study found that RFS and OS were significantly improved in the addition of chemotherapy, especially in patients with clinical-stage IA2, IB, and IIA with para-metric invasion, residual tumor and/or lymph node involvement. This study found that RT had better outcomes in RFS and OS, RT also had lesser hematologic toxicity and non-hematologic toxicity. After all, it is prudent to take into account the adverse events as well as the QOL for long-term survivors. CONCLUSION: Adjuvant RT shows a better outcome in RFS and OS. CRT is often associated with greater hematological and non-hematological toxicities. Further high-quality randomized clinical trials with larger sample size comparing the efficacy and toxicity of adjuvant CRT with RT are recommended.

Neoadjuvant camrelizumab plus chemotherapy for locally advanced cervical cancer (NACI Study): a study protocol of a prospective, single-arm, phase II trial

IntroductionNeoadjuvant chemotherapy (NACT) is an emerging approach for locally advanced cervical cancer (LACC). However, the clinical response and postoperative adjuvant radiation or chemoradiation trimodality treatment resulted in controversy. PD-1 inhibitors...

Prognostic Value of Lymphovascular Invasion in Patients With Pyriform Sinus Carcinoma Treated With Surgery Plus Adjuvant Chemo-/Radiotherapy.

We aimed to determine the prognostic value of lymphovascular invasion (LVI) in pyriform sinus carcinoma (PSC) after primary surgery with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Patients who underwent primary surgery at our institution between 2000 and 2018 were included in this study and retrospectively analyzed. The endpoints were locoregional recurrence (LRR), distant metastasis (DM), and disease-specific survival (DSS). We reviewed 117 patients with PSC. LVI was identified in 29 patients (24.8%). The 5-year LRR rate, DM rate, and DSS rate were 29.4%, 31.7%, and 45.9%, respectively. Tumors with LVI were associated with a significantly higher LRR (P = 0.002, HR 3.678, 95% CI 1.646-8.218) and DM (P = 0.003, HR 3.666, 95% CI 1.543-8.709) and a lower DSS (P = 0.001, HR 2.814, 95% CI 1.519-5.213) in multivariate analysis. LVI is a significant predictor of poor prognosis in patients with PSC treated with surgery plus adjuvant RT/CCRT.

Evaluation of non-hematologic toxicity in patients with cervical cancer after Type 3 radical hysterectomy followed by concurrent chemoradiotherapy: a retrospective study.

To investigate the safety of concurrent chemoradiotherapy after Type 3 radical hysterectomy, focusing on non-hematologic toxicity. Between January 2010 and December 2017, 236 patients diagnosed with cervical cancer Stages IB1-II (FIGO2008) and who had undergone Type 3 radical hysterectomy at the Jikei Medical University School-related four hospitals were included. Of these 236 patients, 134 had undergone adjuvant concurrent chemoradiotherapy after Type 3 radical hysterectomy (radical hysterectomy + concurrent chemoradiotherapy group), and 102 received no adjuvant therapy after Type 3 radical hysterectomy (radical hysterectomy group). The frequency of non-hematologic toxicities, especially lymphedema, pelvic infection, renal dysfunction, ileus and diarrhea, was investigated in the radical hysterectomy + concurrent chemoradiotherapy and radical hysterectomy groups using univariate and multivariate analyses. In these analyses, age, extent of lymph node dissection and preoperative clinical stage were included as risk factors for five complications. The risk factors for grade ≤ 2 adverse events were statistically evaluated. The frequency of lower extremity lymphedema (22 vs. 10%), renal dysfunction (13 vs. 3%), and diarrhea (13 vs. 0%) was significantly higher in the radical hysterectomy + CRRT group than that in the radical hysterectomy group. Logistic regression analysis revealed that adjuvant concurrent chemoradiotherapy significantly affected the occurrence of grade ≥ 2 lymphedema (P < 0.01) and renal dysfunction (P < 0.01). Concurrent chemoradiotherapy after Type 3 radical hysterectomy is associated with a higher incidence of renal dysfunction, lower extremity lymphedema and diarrhea. A more appropriate adjuvant therapy needs to be established.

Low albumin-to-alkaline phosphatase ratio is associated with inferior prognosis in patients with head and neck cancer underwent concurrent chemoradiation: A propensity score-matched analysis.

Low albumin-to-alkaline phosphatase ratio (AAPR) is associated with tumor progression and poor survival outcome in some malignancies. We aimed to determine the prognostic value of AAPR in head and neck cancer (HNC) patients underwent concurrent chemoradiotherapy (CCRT). We retrospectively reviewed medical records of 342 patients with HNC treated with definitive or adjuvant CCRT from 2007 to 2017. Receiver-operator characteristic curve assessed the cut-off value and predictive accuracy of AAPR for disease progression. Propensity score-matched (PSM) method was performed to balance baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). The median follow-up duration was 40 months. The optimal cut-off level of AAPR was 0.523. In the PSM cohort, an AAPR < 0.523 was related to worse PFS and OS (PFS: Hazard ratio [HR], 1.936; 95% confidence interval [CI], 1.212 to 3.249; P = 0.001 and OS: HR, 1.832; 95% CI, 1.117 to 3.478; P = 0.02) compared with those with an AAPR ≥ 0.523. AJCC stage IVA-B also showed poor survival outcome compared with patients with AJCC stage II--III (PFS: HR, 1.855; 95% CI, 1.173 to 2.933; P = 0.008 and OS: HR, 1.905; 95% CI, 1.131 to 3.211; P = 0.015). HNC patients with low AAPR independently have worse survival outcomes than do high AAPR patients. These findings might help physicians predict treatment outcome and guide treatment strategy in patients with HNC underwent CCRT.

Evaluation of Late Toxicities in Postoperative Cases of Oral Cavity Cancer Treated by Intensity-Modulated Radiotherapy (IMRT): A Retrospective Cohort Study

Introduction: Surgical intervention serves as the primary treatment modality for operable oral cavity cancer. However, patients with locally advanced disease or unfavourable prognostic factors often require adjuvant Radiotherapy (RT) with or without concurrent Chemotherapy (CT). Advanced radiation techniques, such as Intensity-Modulated Radiotherapy (IMRT), have shown potential in minimising radiation-related toxicities while ensuring effective tumour control. Aim: To assess common late toxicities, namely xerostomia, dysphagia, and hoarseness, in patients with postoperative Squamous Cell Carcinoma (SCC) of the oral cavity, who received adjuvant RT or concurrent Chemo-Radiotherapy (CRT) utilising IMRT with a Simultaneous Integrated Boost (SIB) approach. Materials and Methods: A retrospective cohort study was conducted in the Department of Radiotherapy at IMS, BHU, Varanasi, Uttar Pradesh, India, from June 2018 to December 2021. Study was done using the medical records of 62 patients with SCC of the oral cavity and received adjuvant radiation by the IMRT technique with or without concurrent CT. Late toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software version 28.0, and a logistic regression model was used to establish the association between Organ-At-Risk (OAR) doses and the development of late toxicities. Results: The median age of the study participants was 45 years (range: 25-68), and 95.2% (n=59) of the patients were male. A total of 62 patients (59 male, 3 female) were included. The median follow-up duration was 21.5 months. At two years, the cumulative incidence of xerostomia, dysphagia, and hoarseness was 28.5% (n=8), 21.4% (n=6), and 28.5% (n=8), respectively. Logistic regression showed that both the D mean of &gt;26 Gy to the contralateral parotid (HR=4.32; 95% CI, 1.03- 18.05; p=0.045) and the D mean of &gt;26 Gy to the contralateral Submandibular Gland (SMG) (HR=6.41; 95% CI, 1.48-27.81; p=0.013) were significantly associated with the incidence of xerostomia. The D mean of &gt;47 Gy to the pharyngeal constrictors (HR=17.89; 95% CI, 3.15-101.62; p=0.001) and the D mean of &gt;50 Gy to the larynx (HR=5.77; 95% CI, 1.82-18.24; p=0.003) had a significantly high risk of dysphagia and hoarseness, respectively. Conclusion: Adjuvant IMRT resulted in acceptable rates of late toxicities in oral cancer. Doses to the contralateral parotid and SMGs, pharyngeal constrictors, and larynx had a significant impact on late xerostomia, dysphagia, and hoarseness, respectively.

Human papilloma virus associated primary vaginal adenocarcinoma

Primary vaginal adenocarcinoma associated with human papillomavirus (HPV) infection is extremely rare. We report a case of primary adenocarcinoma of the vagina associated with human papilloma virus successfully treated with anterior pelvic exenteration and adjuvant concurrent chemoradiation therapy. A 51-year-old postmenopausal woman (gravida 1, para 1) presented with intermittent vaginal bleeding and pelvic pain. She was found to have a 5 × 5 cm necrotic tumor took up the vaginal. She had no previous history of antenatal exposure to diethylstilbestrol (DES). Pelvic magnetic resonance imaging (MRI) demonstrated a 4.8 × 6.0 cm mass in the vaginal canal, an 1.1 × 2.6 cm mass at the urinary bladder dome and a 1.1 cm irregular lymph node at the right external iliac chain with increased fluorodeoxyglucose (FDG) uptake from Fused whole-body positron emission tomography-computed tomography (PET-CT). Based on clinical investigations, the patient was diagnosed with a primary adenocarcinoma of vagina, staged International Fedestration of Gynecology and Obstetrics (FIGO) IVa. Anterior pelvic exenteration, simple vulvectomy, total vaginectomy, both pelvic lymph node dissection, and para-aortic lymph node dissection with ileal conduit urinary diversion (Bricker’s operation) was done. Histologically primary vaginal HPV type 16-associated adenocarcinoma was confirmed. Both obturator lymph node was positive for metastasis. Postoperatively, the patient received weekly cisplatin regimen administered with a dose of 40 mg/m2 on day 1 of external radiation therapy (RT), 1 to 4 hours before RT initiation. External beam pelvic RT dose prescription to the whole pelvis was 59.4 Gy in 33 fractions at the isocenter. But, after total dose of 43.2 Gy, patient complained severe bowel habit change and discontinued further treatment. The patient remains free from recurrence 8 months after initial surgery. In the lack of information and comparative analysis of management options for the more unusual and rare varieties of primary vaginal neoplasms in the literature, this suggests the possibility that surgical treatment may be preferentially selected on a case-by-case basis.