Cycles Of Concurrent Chemotherapy Research Articles

Phase 2 study of concurrent cisplatin, capecitabine and celecoxib with radiotherapy in patients with carcinoma of the oesophagus.

e16078 Background: Oesophageal cancer is the fourth common cause of cancer-related deaths in India. Definitive Chemoradiotherapy is standard for non-metastatic Squamous cell carcinoma of the oesophagus cancer. Chemoradiotherapy when given as definitive treatment is more effective than radiotherapy or chemotherapy alone. This treatment is usually offered to patients who are unsuitable for surgery. Unsuitability for surgery might be due to the extent of disease precluding the likelihood of a curative resection, or because the patient is physiologically not fit for surgery because of comorbidities or poor performance status. The aim of the present study was to analyse the effect of definitive concurrent chemo-radiotherapy in oesophageal cancer patients and assessment of toxicity profile and response. Methods: In the present Phase II study total 22 patients were recruited who had non-metastatic histologically confirmed carcinoma of the oesophagus selected for definitive chemoradiotherapy were enrolled. Chemotherapy consisted of three-weekly cycles of Inj. Cisplatin 60 mg/m2 given on D1, Tab. Capecitabine 625 mg/m2 given BD on D1-D21, and Tab. Celecoxib 200mg given BD on D1-D21. The planned protocol involved four cycles of concurrent chemotherapy. Radiotherapy in a dose of 50.4 Gy in 28 fractions was initiated on D1 of the second cycle of concurrent chemotherapy, or latest by D1 of the third cycle of concurrent chemotherapy. Results: In this Phase 2 study, 22 patients with a mean age of 55.68 ± 11.23 years, were treated. The tumor length averaged 6 ± 2.25 cm, with most common Stage III (52.17%), followed by Stage II (34.78%), Stage I (8.69%), and Stage IVA (4.34%). Grade 3 dysphagia was predominant (56.52%), followed by Grade 2 (34.78%), Grade 1 (4.35%), and Grade 4 (4.35%). During treatment, notable grade 1-2 toxicities included esophagitis(68%), fatigue(63%), nausea (54%), neutropenia (31%), anemia (22%), mucositis(18%), diarrhoea(13%), dermatitis(9%). There was gradual decline in the severity of dysphagia of all patients. Of the 8 patients evaluated for response with a median follow up of 12 months, the complete response rate was 25%, partial response rate was 25% and 37.5% showed stable disease whereas 12.5% developed progressive disease. The median overall survival is yet to be estimated. Conclusions: A notable clinical response, indicating a substantial treatment effect was observed. While some treatment-related toxicities were present, This approach shows potential in the treatment of oesophageal carcinoma. However, this study is still ongoing and it would be hasty to draw definitive conclusions.

A phase II study of radiotherapy combined with docetaxel, cisplatin, and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer.

4029 Background: Recently, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery for patients with esophageal cancer have resulted in favorable prognosis, but extended radical esophagectomy with two-field or three-field (neck, mediastinum, and abdomen) lymph node dissection remains a standard treatment. However, there is recurrence in 30-50% of patients who have undergone an operation and there is loco-regional recurrence in 40-55% of patients with postoperative recurrence. The efficacy and safety of chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer have been reported, and the survival outcome has been improved; however, the median progression-free survival period according to past reports was 10 to 14 months, which was not enough. Recently, RT with docetaxel (DOC), cisplatin (CDDP) and 5-FU has shown better results than conventional standard treatment (CDDP+5-FU +radiotherapy) for primary esophageal cancer. The purpose of the phase II study was to evaluate the superior of definitive radiotherapy with DOC, CDDP and 5-FU to the standard treatment in patients with loco-regional recurrent esophageal cancer after curative resection. Methods: Between 2015 and 2023, this open-label, single-arm, phase II study of radiotherapy (60 Gy/30 fractions/6 weeks without prophylactic region) combined with chemotherapy consisting of 3 cycles of DOC (35 mg/m2), CDDP (40 mg/m2) and 5-FU (400 mg/m2/24 h for 5 days) for patients with postoperative loco-regional recurrent esophageal cancer was conducted at a single institution. The primary endpoint was progression-free survival rate. This trial was considered positive if median progression-free survival period was 24.0 months or more, which meaning superiority over conventional standard treatment. The secondary endpoints were overall survival rate and adverse events. This trial was registered with UMIN Clinical Trials Registry (UMIN000019269) and Japan Registry of Clinical Trials (jRCTs021200009). Results: A total of 29 patients were enrolled in this study. The regimen was completed in all the patients. The median observation period for survivors was 60 months (IQR, 30.0-75.5 months). The 5-year progression-free survival rate was 56.2% (95% CI = 37.4-75.0%) with a median progression-free survival period of 62.0 months (95% CI = 35.2-64.7 months). Only 2 patients showed grade 4 hematologic adverse events during chemoradiotherapy, and they had to be performed reduced chemotherapy; however, they also completed 3 cycles of concurrent chemotherapy. Grade 2 or higher late toxicity was not observed in any patients. Conclusions: The present protocol of radiotherapy combined with DOC, CDDP and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. It might be better than conventional treatment. Clinical trial information: UMIN000019269.

The association analysis between fatigue and body composition loss in patients with nasopharyngeal carcinoma during radiotherapy: An observational longitudinal study

PurposeThis study aimed to reveal the association of fatigue with weekly changes in the body composition in patients with nasopharyngeal carcinoma (NPC) and identified the independent strength. MethodsFour body composition indexes and fatigue were assessed before treatment (T0, baseline) and once a week throughout radiotherapy (T1-T7). Generalized additive mixed models (GAMMs) were used to explore the trajectories and longitudinal relationships of fatigue and weekly changes in body composition. The marginal structural model (MSM) was used to control the effect of depression and anxiety. ResultsThe trajectories of fatigue in 105 participants reached a peak in the fifth week, and changes in body composition started appearing from the second week. Four body composition indexes, weight, body mass index (BMI), body fat rate, and lean body weight loss weekly were positively associated with fatigue. High magnitude of effects was revealed when anxiety and depression were controlled as time-dependent confounders. The positive associations with fatigue were manifested in patients aged >53 years, those with senior high and above education, no drinking, >5000 Y/month of family inflow, ≥ stage III, or those receiving a dose of ≥70 Gy, ≥3 cycles of induced chemotherapy, and ≤1 cycle of concurrent chemotherapy. ConclusionsLoss of weight, BMI, body fat rate, and lean body weight could be used to independently evaluate the development of fatigue in patients with NPC during radiotherapy. Positive associations between fatigue and weekly body composition loss were found in patients with certain characteristics.

High pre-chemoradiotherapy pan-immune-inflammation value levels predict worse outcomes in patients with stage IIIB/C non-small-cell lung cancer

Background and objectivesWe explored the prognostic usefulness of the pan-immune-inflammation value (PIV) in patients with stage IIIB/C non-small-cell lung cancer (NSCLC) who underwent concurrent chemoradiotherapy (CCRT).Methods and patientsFor all patients, the PIV was calculated using platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) measures obtained on the first day of CCRT: PIV = P × M × N ÷ L. Using receiver operating characteristic (ROC) curve analysis, we searched for the existence of an ideal cutoff that may partition patients into two groups with unique progression-free- (PFS) and overall survival (OS) results. The primary endpoint of this retrospective cohort research was to determine whether there were any significant relationships between pretreatment PIV measures and post-CCRT OS outcomes.ResultsThe present research included a total of 807 stage IIIB/C NSCLC patients. According to ROC curve analysis, the ideal PIV cutoff was 516 [area under the curve (AUC): 67.7%; sensitivity: 66.4%; specificity: 66.1%], which divided the whole cohort into two: low PIV (L-PIV: PIV < 516; N = 436) and high PIV (H-PIV: PIV ≥ 516; N = 371). The comparisons between the PIV groups indicated that either the median PFS (9.2 vs. 13.4 months; P < 0.001) or OS (16.7 vs. 32.7 months; P < 0.001) durations in the H-PIV group were substantially inferior to their L-PIV counterpart. Apart from the H-PIV (P < 0.001), the N3 nodal stage (P = 0.006), IIIC disease stage (P < 0.001), and receiving only one cycle of concurrent chemotherapy (P = 0.005) were also determined to be significant predictors of poor PFS (P < 0.05, for each) and OS (P < 0.05, for each) outcomes in univariate analysis. The multivariate analysis findings revealed that all four variables had independent negative impacts on PFS (P < 0.05, for each) and OS (P < 0.05, for each).ConclusionsThe findings of this hypothesis-generating retrospective analysis claimed that the novel PIV was an independent and steadfast predictor of PFS and OS in stage IIIB/C NSCLC patients.

The Prognostic Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) in Stage IIIC Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy.

We sought to determine the prognostic value of the newly developed Global Immune-Nutrition-Inflammation Index (GINI) in patients with stage IIIC non-small cell lung cancer (NSCLC) who underwent definitive concurrent chemoradiotherapy (CCRT). This study was conducted on a cohort of 802 newly diagnosed stage IIIC NSCLC patients who underwent CCRT. The novel GINI created first here was defined as follows: GINI = [C-reactive protein × Platelets × Monocytes × Neutrophils] ÷ [Albumin × Lymphocytes]. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal pre-CCRT GINI cut-off value that substantially interacts with the locoregional progression-free (LRPFS), progression-free (PFS), and overall survival (OS). The optimal pre-CCRT GINI cutoff was 1562 (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%; Youden index: 0.406). Patients presenting with a GINI ≥ 1562 had substantially shorter median LRPFS (13.3 vs. 18.4 months; p < 0.001), PFS (10.2 vs. 14.3 months; p < 0.001), and OS (19.1 vs. 37.8 months; p < 0.001) durations than those with a GINI < 1562. Results of the multivariate analysis revealed that the pre-CCRT GINI ≥ 1562 (vs. <1562), T4 tumor (vs. T3), and receiving only 1 cycle of concurrent chemotherapy (vs. 2-3 cycles) were the factors independently associated with poorer LRPS (p < 0.05 for each), PFS (p < 0.05 for each), and OS (p < 0.05 for each). The newly developed GINI index efficiently divided the stage IIIC NSCLSC patients into two subgroups with substantially different median and long-term survival outcomes.

Toxicity, Disease Control, and Survival Outcomes of Intensified Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Single-Institution Study.

The standard treatment regimen of preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) is still controversial. The purpose of this study was to analyze the efficacy and safety of preoperative intensive CRT in our institution. A retrospective data collection and analysis of 181 LARC patients receiving oxaliplatin (85%) of standard doses in capecitabine-based preoperative CRT and two additional cycle of neoadjuvant chemotherapy between the end of concurrent CRT and surgery. The compliance of the preoperative CRT was satisfactory with 99.4%patients completed radiotherapy and 97.19%patients completed all 2 cycles of concurrent chemotherapy. Except for 20 patients diagnosed clinical complete remission (cCR) managed according to watch and wait strategy, 160 patients received R0 radical surgery. The pathological complete response (pCR) rate was 23.75% (38/160) and tumor regression grade (TRG) 0/1 was 40% (72/180). In terms of tumor downstaging, 89 (55.63%) had T downstaging while 115 (71.88%) had N downstaging. The 1-overall survival (OS),2-OS,3-OS and 5-OS were 98.7%, 96.5%, 91.4% and 81.5%, respectively. The total rate of sphincter preservation was 86.25% (138/160) and the rate of patients with low rectal cancer was 73.0% (54/74) without affecting local control rates and survival rates. Both acute adverse reactions to preoperative CRT and postoperative complications were tolerable and controllable. In this retrospective study, preoperative intensive CRT of patients with LARC achieved satisfied disease control and survival outcomes and well acquired the sphincter retention rate in recent years in our institution. On the basis of these findings, a Phase III study to definitively test the intensified preoperative CRT strategy is warranted.

Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study.

Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This intensive treatment regimen increases acute toxicities, which could negatively impact patients' nutritional status. We conducted this prospective, multicentre trial to investigate the effects of IC and CCRT on nutritional status in LA-NPC patients, so as to provide evidence for further study of nutritional intervention, which was registered in ClinicalTrials.gov (NCT02575547). Patients with biopsy-proven NPC and planned for IC+CCRT were recruited. IC entailed two cycles of 3-weekly docetaxel 75mg/m2 and cisplatin 75mg/m2 ; CCRT entailed two to three cycles of 3-weekly cisplatin 100mg/m2 depending on the duration of radiotherapy. Nutritional status and quality of life (QoL) were assessed pre-IC, post-cycles one and two of IC, W4 and W7 of CCRT. Primary endpoint was the cumulative proportion of ≥ 5.0% weight loss (WL5.0 ) by the end of treatment (W7-CCRT). Secondary endpoints included body mass index, NRS2002 and PG-SGA scores, QoL, hypoalbuminaemia, treatment compliance, acute and late toxicitiesand survivals. The associations between primary and secondary endpoints were also evaluated. One hundred and seventy-one patients were enrolled. Median follow-up was 67.4 (IQR: 64.1-71.2) months. 97.7% (167/171) patients completed two cycles of IC, and 87.7% (150/171) completed at least two cycles of concurrent chemotherapy; all, except one patient (0.6%), completed IMRT. WL was minimal during IC (median of 0.0%), but increased sharply at W4-CCRT (median of 4.0% [IQR: 0.0-7.0%]) and peaked at W7-CCRT (median of 8.5% [IQR: 4.1-11.7%]). 71.9% (123/171) of patients recorded a WL5.0 by W7-CCRT, which was associated with a higher malnutrition risk (NRS2002≥3 points: 87.7% [WL≥5.0%] vs 58.7% [WL<5.0%], P<0.001) and requirement of nutritional intervention (PG-SGA≥9 points: 82.0% [WL≥5.0%] vs 66.7% [WL <5.0%], P=0.038). The median %WL at W7-CCRT was higher in patients who suffered from ≥ G2 mucositis (9.0% vs 6.6%, P=0.025) and xerostomia (9.1% vs 6.3%, P=0.003). Besides, patients with cumulative WL5.0 also reported a higher detriment on QoL at W7-CCRT compared with patients without, with a difference of -8.3 points (95% CI [-15.1, -1.4], P=0.019). We observed a high prevalence of WL among LA-NPC patients who were treated with IC+CCRT, which peaked during CCRT, and had a detriment on patients' QoL. Our data support the need to monitor patient's nutritional status during the later phase of treatment with IC+CCRT and inform on nutritional intervention strategies.

High-Dose Versus Standard-Dose Intensity-Modulated Radiotherapy With Concurrent Paclitaxel Plus Carboplatin for Patients With Thoracic Esophageal Squamous Cell Carcinoma: A Randomized, Multicenter, Open-Label, Phase 3 Superiority Trial

The standard dose (SD) of definitive concurrent chemoradiotherapy (dCRT) remains 50.4 Gy in patients with esophageal cancer; a higher dose, when applied with conventional radiation therapy techniques, increases toxicities without improving survival. We investigated whether a high dose of 59.4 Gy using intensity-modulated radiation therapy (IMRT) would improve survival without increasing toxicities. Patients with inoperable thoracic esophageal squamous cell carcinoma (SCC) referred for dCRT were randomly assigned (1:1) to high-dose (HD) IMRT (59.4 Gy) or SD IMRT (50.4 Gy). Chemotherapy consisted of 6 cycles of concurrent weekly paclitaxel and carboplatin and a maximum of 2 cycles of consolidation chemotherapy. Nutritional intervention was implemented for patients with malnutrition on the basis of nutritional screening. The primary endpoint was median overall survival (mOS). Analyses were by modified intention to treat. Between April 30, 2016, and April 30, 2019, 167 patients were enrolled at 9 participating centers in China. Seventy-one patients in the HD and 73 patients in the SD groups were included in the analysis; 86.8% of the patients completed radiation therapy and 70.1% received 5 or 6 cycles of concurrent chemotherapy. The median follow-up was 36.0 months. The mOS was 28.1 and 26.0 months in the HD and SD arms, respectively (P=.54). A total of 7 treatment-related deaths were observed. Grade 3 or worse treatment-related toxicities were observed in 62% and 68.5% of the patients in the HD and SD arms, respectively (P=.675). For patients with inoperable thoracic esophageal SCC, a dose of 59.4 Gy did not improve survival compared with the SD of dCRT using IMRT.

Intra-Treatment Tumor Apparent Diffusion Coefficient, a Quantitative Imaging Metric, is Associated with Neck Nodal Recurrence in De-Escalated Treatment of HPV-Positive Oropharyngeal Cancer (OPC)

<h3>Purpose/Objective(s)</h3> De-escalation strategies for the treatment of HPV-associated OPC show promise for effective, less toxic treatment. However, identifying accurate markers of more aggressive subsets of HPV OPC remains challenging. The 30 Reduction in Radiation for OPC (ROC) trial prospectively used intra-treatment ¹⁸F-FMISO imaging to selectively de-escalate patients to 30Gy chemoradiotherapy, however, a subset of patients still developed nodal recurrence. We hypothesized that diffusion-weighted (DW) MRI-derived quantitative imaging metrics, such as apparent diffusion coefficient (ADC), a surrogate marker of tumor cellularity based on water diffusion patterns, might help identify patients at high risk of recurrence and enable broader use of de-escalation strategies<b>.</b> <h3>Materials/Methods</h3> The 30 ROC trial enrolled patients with p16-positive OPC, cT0-2, N1-2c (AJCC 7^th ed). All patients had pre-treatment ¹⁸F-FMISO (fluoromisonidazole) PET scan and those with baseline nodal hypoxia underwent a 2^nd intra-treatment scan. All patients underwent primary site surgery where negative margin was not required. All patients had gross neck nodal disease. Those with intra-treatment resolution of nodal hypoxia or without initial hypoxia were de-escalated to 30Gy (non-hypoxic group) with 2 cycles of concurrent chemotherapy, while those with persistent radiographic hypoxia (hypoxic group) were treated to 70Gy. Standard T1, T2 weighted, and multiple b-value DW-MRI data were acquired pre-treatment and weekly during the first 4 weeks of treatment. Two radiation oncologists delineated nodal tumor regions of interest (ROIs) in a blinded fashion with ITK-SNAP on DW images (b= 0 s/mm²). Multiple b-value DW data were fitted to a monoexponential model to calculate ADC (mm²/s). The data analysis was performed on ROIs and voxel-wise using the in-house developed tool MRI-QAMPER. Standard statistical analysis was performed using MRI and clinical response data based on RECISTv1.1 provided by a radiologist. <h3>Results</h3> 158 patients were enrolled, of whom 95 had pre-treatment DW-MRI data available with tumor ROI with ADC values. Based on overall ¹⁸F-FMISO imaging, 12.6% (12/95) exhibited persistent hypoxia and 87.4% (83/95) had resolved/no hypoxia. All patients with nodal recurrences were in the de-escalated non-hypoxic group (8/83). Pre-treatment ADC was not different between overall hypoxic and non-hypoxic groups. Among de-escalated patients, those who developed nodal recurrence exhibited significantly different intra-treatment ADC at week 3 (before completing 30Gy) relative to those who did not recur (P<0.05, Wilcoxon rank-sum test). <h3>Conclusion</h3> The quantitative imaging metric, ADC, reflects both the restricted and hindered Brownian motion of water molecules in tumor tissue. Thus, ADC may be a useful intra-treatment marker to identify patients at risk for nodal recurrence to benefit from the incorporation of an upfront planned neck dissection after 30Gy as part of the de-escalation strategy.

Four-Phase, Definitive Chemoradiation for a Real-World (Poor Risk and/or Elderly) Patient Population With Locally Advanced Non-small Cell Lung Cancer.

IntroductionWith the incorporation of modernized radiotherapy, chemotherapy, and immunotherapy, treatment outcomes have improved for patients with locally advanced, unresectable diseases. Elderly or poor performance status patients comprise more than half of non-small cell lung cancer (NSCLC) patients, but they are often underrepresented or excluded in clinical trials. Split-course concurrent chemoradiotherapy can be an effective treatment, showing good adherence and a favorable toxicity profile for unresectable, locally advanced NSCLC.MethodWe identified locally advanced NSCLC cancer patients via a single institution retrospective study. Patients were treated using a four-phase, split-course external beam radiotherapy approach with concurrent chemotherapy. The primary endpoints analyzed were completion rate, incidence, and severity of treatment-related toxicities, progression-free survival (PFS), and median overall survival (OS).ResultsThirty-nine locally advanced lung cancer patients were treated with split-course chemoradiation (CRT). The median age at diagnosis was 73 years old. Seventeen patients had an Eastern Cooperative Oncology Group (ECOG) performance score of 2. Twenty-three patients had a clinical diagnosis of chronic obstructive pulmonary disease (COPD), and 10 patients were on home oxygen at the time of diagnosis. All patients completed 6000 centigrays (cGy) of radiation, and 95% of the patients completed at least three cycles of concurrent chemotherapy. No patients experienced grade 3 to 5 acute thoracic toxicities. Overall median survival was 12.7 months, and PFS was 7.5 months.ConclusionOur retrospective analysis of 39 poor risk and/or elderly patients with locoregional NSCLC treated with concurrent CRT via a split-course regimen suggests favorable oncologic outcomes and superb treatment completion rates and toleration.

Definitive chemoradiotherapy +/- induction chemotherapy in esophageal cancer: A real-world experience.

e16072 Background: The SEER 5-year overall survival rate for all stages of esophageal cancer (EC) was 25% in 2019. Definitive chemoradiation (CRT) remains the primary treatment approach for locally advanced EC in the US, however, there are data to support use of induction chemotherapy (CT) in addition to CRT, particularly in adenocarcinoma (AC) histology. The purpose of our study was to assess outcomes in EC patients treated with definitive CRT (+/- induction) to determine which prognostic factors predicted for better survival in a recent, real-world cohort of patients, including those with limited stage IV disease. Methods: This retrospective study included Stages II-IVB (AJCC 8th ed.) EC patients treated with definitive CRT (radiation dose of ≥40 Gy and at least two cycles of concurrent CT [+/- induction CT, +/- esophagectomy]) at our institution between 2008 and 2020. To analyze prognostic factors and estimate OS, univariate models (UVA) and a multivariate (MVA) Cox proportional hazards regression model including age, Stage (II, III, IVA, IVB), AC vs. SCC, esophagectomy, ECOG performance status (PS), and induction CT were performed. Results: Of the 183 patients treated with definitive CRT, 18 were stage II, 119 stage III, 21 stage IVA, and 25 stage IVB. There were 45 SCC and 138 AC patients (Table). Prognostic factors associated with prolonged OS on MVA included lower PS (p&lt;0.01) and esophagectomy (p = 0.05). Stage IVA was associated with shorter survival (p&lt;0.01). Induction CT (delivered in 53% of AC, 31% SCC) was associated with improved survival on UVA (p=0.04), but not MVA (p = 0.08). By histology, 5-year survival rate was 42.7% and 18.2% for AC and SCC, respectively. Conclusions: At our institution, those who received an esophagectomy and those with lower ECOG scores had better survival. The 5-year survival rate was higher for AC patients compared to SCC, with more AC patients receiving esophagectomy and induction CT (significant on UVA, but not MVA). The 5-year survival rate for AC in our study was nearly identical to that seen in the CROSS trial (Shapiro et al. 2015) AC cohort but included &gt;25% stage IV patients. This modern cohort also included poor PS (ECOG≥2) patients (9.2% AC and 13.6% SCC), suggesting induction CT, in addition to pre-operative CRT + surgery, may have added benefit in a real-world practice. Thus, further prospective study is needed.[Table: see text]

ACUTE TOXICITY PROFILE OF CONCURRENT CHEMORADIATION IN CARCINOMA CERVIX WITH THE INTEGRATION OF BRACHYTHERAPY DURING EXTERNAL BEAM RADIATION THERAPY

Background: Concurrent chemoradiation with weekly cisplatin is the treatment of choice in a case of carcinoma cervix. Prolonging treatment time is detrimental to disease control. When brachytherapy is scheduled during external beam radiation therapy (EBRT), treatment time can be shortened signicantly thereby improving local control. As the delivery of radiation with brachytherapy is uniform and spares normal tissues it reduces the acute toxicities. In this study, we aimed to study the acute toxicities associated with this unique scheduling of brachytherapy along with EBRT. Fifty patients with carcinoma cervix between stage IIA to IIIB treated at our institution with chemo-Methods: radiation were included in the study. Concurrent chemotherapy was delivered using weekly cisplatin (40mg/m2) for 5 cycles. EBRT was delivered using four eld box technique. HDR brachytherapy was introduced after 3rd week of EBRT. Brachytherapy was delivered in 3 fractions each 8.5Gy at the end of the 3rd, 4th, and 5th week. Acute RTOG toxicities were assessed during the treatment and one week post treatment. The median age of the study population is 45 years. Eighty four percent ofResults: patients received 4 or more cycles of concurrent chemotherapy, whereas 16% of patients received only 3 cycles of concurrent chemotherapy. Most common toxicity observed in the current study population is diarrhea followed by vomiting. Most toxicities are of RTOG grade 0 or 1 and none of the patients developed grade 4 toxicity. Only two patients developed grade 3 diarrhea and one patient developed grade 3 neutropenia. Integrating brachytherapy schedule along with EBRT decreasesConclusion: overall treatment time with an acceptable acute toxicity prole.

One Cycle of Concurrent Chemotherapy vs. Two Cycles of Concurrent Chemotherapy With Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer.

BackgroundThe optimal number of concurrent chemotherapy cycles during thoracic radiotherapy (RT) in patients with limited stage-small cell lung cancer (LS-SCLC) is not well defined. The purpose of this study was to evaluate the impact of the number of concurrent chemotherapy cycles on prognosis of LS-SCLC.Material and MethodsPatients with LS-SCLC treated with concurrent chemo-radiotherapy from May 2008 to December 2020 in our hospital were retrospectively analyzed. The prescribed radiation dose was 60Gy administrated with conventional RT in 30 fractions within 6 weeks. The prognostic role of cycle number of chemotherapy administrated concurrently with RT were analyzed. All patients were followed up at one month after the treatment, then once every three months until two years after the treatment, and every six months thereafter. Propensity score matching (PSM) was performed to reduce confounding factors. The primary endpoint was overall survival (OS). Survival analysis was performed with Kaplan-Meier and multivariate analysis was performed with Cox regression model.ResultsAmong the 370 patients who received radical radiotherapy, 206 patients received concurrent chemo-radiotherapy and were included for the analysis. Multivariate analysis showed that stage and PCI were independent prognostic factors for OS. The median OS in patients who received one cycle and two cycles of chemotherapy concurrently with RT were 32.9 months and 31.6 months, respectively (P = 0.241). And the median PFS were 20.6 months and 18.4 months, respectively (P = 0.764). After PSM, no statistical differences in OS and PFS were observed between patients who received one cycle and those who received two cycles of concurrent chemotherapy.ConclusionTwo cycles of concurrent chemotherapy during RT were not necessarily superior compared to one cycle in LS-SCLC. The optimal cycle number of concurrent chemotherapy during RT needs to be further studied.

Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer

Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer. A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel. From May 2015 to September 2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 were male (60%). Fourteen (70%) had squamous cell and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least 1 cycle of consolidation chemotherapy. Within the 6-month time-to-event continuous reassessment method assessment window, no SAEs were reported, and most patients were treated at the highest dose level. Dose level assignment was 52.5 Gy (n=2), 56.25 Gy (n=4), and 60 Gy (n=14). The posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% confidence interval, 1%-18.1%). Acute, nonserious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were 3 (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively. Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted.

Factors predictive of parametrial boost in patients with cervical cancer treated with definitive chemoradiation

ObjectiveThe aim of this study is to identify demographic, clinical, and treatment-related characteristics associated with the prescription of parametrial boost (PMB) in cervical cancer patients undergoing definitive chemoradiation. Materials/MethodsA retrospective chart review of 132 non-metastatic cervical cancer patients treated with definitive chemoradiation from May 2017 to December 2019 was performed. Demographic, clinical, and treatment characteristics were obtained and compared between those who received PMB and those who did not. Clinical outcomes (pelvic recurrence, tumor persistence, distant metastases, and median survival time) were also gathered and compared. Statistical software was used for analysis, with a p < 0.05 considered statistically significant. ResultsOf the 132 patients included in the analysis, 74 (56%) received PMB of 10 Gy in five daily fractions and 58 (44%) did not. Patients who received PMB were more likely to have pelvic sidewall invasion at the time of diagnosis (OR 4.053, 95% CI 1.163–14.13, p < 0.05) and received more cycles of concurrent chemotherapy during whole pelvis irradiation (OR 2.149, 95% CI 1.370–3.371, p < 0.05). At a median follow-up of 24 months, there was no statistically significant difference in the crude rates of pelvic recurrence, tumor persistence, distant metastasis, and median survival between the two groups. ConclusionPresence of pelvic sidewall invasion at diagnosis and increased number of chemotherapy cycles were predictive of administering PMB after whole pelvis irradiation. There was no significant difference in treatment outcomes for those with and without PMB.

The 30 ROC trial: Precision intra-treatment imaging guiding major radiation reduction in human papillomavirus related oropharyngeal cancer.

6019 Background: Our previously published proof-of-concept trial using functional imaging to select patient with human papillomavirus (HPV) oropharyngeal carcinoma (OPC) for radiation de-escalation showed promising results. Here we report the outcome of a larger validation trial using the same paradigm where select HPV+ OPC patients received a definitive dose of 30Gy concurrently with chemotherapy and were subsequently observed. Methods: The trial enrolled patients who had p16+, T0-2, N1-N2c, M0 OPC by AJCC 7th TNM. Patients were required to have resection of the primary site (negative margin not required) or core biopsy of lymph node if unknown primary. In addition to standard positron emission tomography (PET), a pre-radiation dynamic 18F-FMISO (fluoromisonidazole) PET was performed to identify hypoxia in gross nodal disease. Patients with evidence of hypoxia ( &gt; 1.2 tumor to muscle standard uptake value on 18F-FMISO) underwent repeat18F-FMISO PET around 2 weeks into radiation. Patients without pre-radiation hypoxia or with resolution of hypoxia on 18F-FMISO PET received 30Gy with 2 cycles of concurrent chemotherapy (cisplatin 100mg/m2 or carboplatin AUC 1.25 x 4 with 5-fluorouracil 2400 mg/m2). Results: From 11/2/17-1/4/21, 158 HPV+ OPC patients consented and were enrolled on trial. Patient characteristics were as follows: male (90%); ages 36-80 years; T-stage T0(26), T1(77), T2(55); N stage N1(19), N2a(15), N2b(95), N2c(29). Of the 114 patients with pre-treatment hypoxia, 24 had persistent hypoxia and received 70Gy. 128 patients were de-escalated to 30Gy and chemotherapy (86% cisplatin). 6 patients withdrew from trial [3 decided to receive standard of care; 3 refused 18F-FMISO PET]. Acute mucositis rates were 11% grade 0, 59% grade 1, and 30% grade 2, respectively. Acute xerostomia rates were 92% grade 1 and 8% grade 2, respectively. Weight loss was infrequent and only 19% complained of grade 1 and 5% complained of grade 2 weight loss. Six patients experienced grade 3 adverse events (diarrhea (2), syncope (2), vasovagal (1), dysphagia (1)). No patients required PEG tubes. With a median follow-up is 12 months (range: 2 months to 40 months), the 1-year locoregional control, distant metastasis-free overall survival rates were 94%, 100%, and 100%, respectively. Among the 30Gy de-escalated patients, none failed in the primary site. 8 patients had recurrent nodal disease underwent successful salvage surgery of which no additional therapy was given to 4 patients. Conclusions: Major de-escalation to 30Gy using patient specific treatment response based on hypoxia resolution resulted in excellent locoregional control with significant toxicity reduction. Updated results along with detailed correlative analysis will be presented. Clinical trial information: NCT03323463.

Verification of Pre-treatment NLR and PLR on the Prognosis of Patients with Locally Advanced Cervical Cancer

Previous studies showed that neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were important prognostic factors for patients with cervical cancer. The purpose of this study was to verify the correlation between pre-treatment NLR, PLR and clinical outcomes in patients with locally advanced cervical cancer. We reviewed 222 cervical cancer patients who underwent definitive concurrent chemoradiotherapy or radiotherapy in 2014 in our institute. The patients were divided into different groups based on the optimal cut-off values of pre-treatment NLR or PLR according to receiver operating characteristic curves. The survival outcomes were calculated with Kaplan-Meier method. Cox proportional hazard model were used for univariate and multivariate analyses. The median follow-up duration was 34 months (range,3-66months). For the whole group, 3-year OS, DFS, LC were 83%, 80%, 91%, respectively. NLR = 1.8 and PLR = 151 were selected as the best cut-off values, respectively. The 3-year OS, DFS and LC in the high NLR group were 82%, 79% and 88%, while the 3-year OS, DFS and LC in the low NLR group were 86%, 85% and 96%, respectively, and the differences were not statistically significant. The 3-year OS, DFS and LC in the high PLR group were 88%, 80% and 91%, while the 3-year OS, DFS and LC in the low PLR group were 79%, 80% and 90%, respectively, and there were also no statistically significant differences between both groups. Univariate analysis showed that FIGO stage, overall treatment time, total dose of brachytherapy, and cycles of concurrent chemotherapy were important prognostic factors for OS of locally advanced cervical cancer. Overall treatment time was significantly corelated with DFS and LC of locally advanced cervical cancer. Multivariate analysis indicated that overall treatment time and total dose of brachytherapy were independent prognostic factors for locally advanced cervical cancer, respectively. There are no significant correlation between pre-treatment NLR or PLR and the survival outcomes of locally advanced cervical cancer in the present study. Further trials will be required to validate whether pre-treatment NLR and PLR are important prognostic factors for locally advanced cervical cancer.

The clinical outcomes of elderly esophageal cancer patients who received definitive chemoradiotherapy

Background:Neoadjuvant chemoradiotherapy (CRT) followed by an esophagectomy is the standard treatment for locally advanced esophageal cancer, but remains a great challenge for elderly patients. Therefore, we aim to evaluate the efficacy of definitive CRT in elderly patients with esophageal cancer.Methods:From December 2007 to October 2017, 40 esophageal cancer patients aged ≥70 years receiving definitive CRT were retrospectively analyzed. All patients received cisplatin-based chemotherapy. Ten patients received standard doses of cisplatin 20 mg/m2 and fluorouracil (5-FU) 800 mg/m2 for 4 days, during the first and fifth weeks of radiotherapy. Eighteen patients received modified doses of cisplatin 16 to 18 mg/m2 and 5-FU 600 to 800 mg/m2. Twelve patients received lower doses of cisplatin 10 to 12 mg/m2 and 5-FU 400 to 600 mg/m2. The endpoints were overall survival (OS), tumor response rate, and treatment compliance.Results:The 3-year OS rate was 28.8% The 3-year OS rates for patients receiving standard, modified, and lower doses were 12.5%, 53.8%, and 0.0%, respectively (p = 0.05). There were 87.5% of patients completing the scheduled radiotherapy dose, along with two cycles of concurrent chemotherapy. The response rate (clinical complete response and partial response rate) was 70.0%. Multivariate analysis revealed that no statistical difference was found in the OS among three groups of chemotherapy dosage. The treatment response was the only independent prognostic factor to OS (p < 0.001).Conclusion:Definitive CRT with dose modification is a feasible, safe, and reasonable treatment for elderly esophageal cancer patients. Achieving a better compliance to CRT via an optimal dose modification of chemotherapy may provide better clinical outcomes and would be the treatment goal for elderly esophageal cancer patients.

Late-course accelerated Hyperfractionation vs. Conventional Fraction Radiotherapy under precise technology plus Concurrent Chemotherapy for Esophageal Squamous Cell Carcinoma: comparison of efficacy and side effects

Background: The accelerated reproliferation of esophageal squamous cell carcinoma (ESCC) after radiation contributes to conventional fraction radiotherapy (CFRT) failure. Late course accelerated hyperfractionated radiotherapy (LCAHFRT) can improve the long-term survival of esophageal cancer patients in China but is associated with a high rate of side effects due to the large exposure field of two-dimensional treatment and drug toxicity. Intensity-modulated radiotherapy (IMRT) can increase the tumor dose while decreasing the normal tissue dose. Therefore, we compared the outcomes and side effects of LCAHFIMRT plus concurrent chemotherapy (CT) and CFIMRT plus CT for ESCC.Methods and Materials: Between 2013 and 2016, 114 eligible patients with ESCC were recruited and randomly assigned to receive LCAHFIMRT+CT (58 patients) or CFIMRT+CT (56 patients) by a linear accelerator (6-MV X-ray) under image guidance. Two cycles of CT with cisplatin and docetaxel were also administered.Results: The complete response (CR) rates were 79.3% and 61.8% in the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.041). The median duration of local control times was 31.0±1.9 months for the LCAHFIMRT+CT group and 24.0±3.3 months for the CFIMRT+CT groups,and the 1-, 2-, and 3-year local control rates were 86.2%, 63.8%, and 41.4% and 85.7%, 51.8%, and 32.1% for the LCAHFIMRT+CT and CFIMRT+CT groups (P=0.240), respectively. The median survival times were 34.0±1.1 months for the LCAHFIMRT+CT group and 28.0.0±3.7 months for the CFIMRT groups,and the 1-, 2-, and 3-year survival rates were 87.9%, 74.1%, and 44.8% and 87.5%, 60.7%, and 39.3% for the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.405). The incidence of side effects was not significantly different between the two groups. Local recurrence and uncontrolled disease resulted in more deaths in the CFIMRT+CT group than in the LCAHFIMRT+CT group (58.9% vs. 39.7%) (P=0.040).Conclusion: For ESCC patients, LCAHFRT delivered by image-guided intensity-modulated techniques Plus Concurrent Chemotherapy with cisplatin and docetaxel keeps safety and high CR rate, as well as local control and long-term survival rates.

1142P - To compare two oral mucosa contouring methods in predicting acute oral mucocitis in nasopharyngeal carcinoma treated with helical tomotherapy

BackgroundThe purpose of this study was to evaluate prediction effect for acute radiation-induced oral mucositis (A-ROM) of two oral mucosa contouring methods in nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy. MethodsA total of 151 AJCC 7th stage II-IVB histologically proven NPC patients receiving radical tomotherapy (TOMO) from Zhejiang Cancer Hospital were included. All patients received 0-4 cycles of platinum-based induction chemotherapy±1-3 cycles of concurrent chemotherapy (all patients received at least one chemotherapy). Oral cavity contour (OCC) and mucosa surface contour (MSC) were applied to radiation treatment plans. A-ROM were prospectively assessed weekly according to RTOG scoring criteria. Absolute DVH data was exported from RayStation V3.0 system. T-test, X2 test, binary logistic regression and ROC curve were used to analyses. ResultsMorbidity of≥3 grade A-ROM was 30.4%. In univariate analysis: V10, V15, V45, V55, V60, V65, V70 of OCC and V15, V55, V60, V65, Dmean of MSC were significant related to≥3 grade A-ROM (Vx, percentage volume of organ received more than Gy, all P0.05). In binary logistic regression analysis, gender, smoking were found significantly related to≥3 grade A-ROM by using OCC (male vs. female : OR=0.070, 95%CI=0.019-0.411, P=0.008 ; smoking vs. non-smoking: OR=15.250, 95%CI=4.421-61.980, P=0.001). For MSC, gender, smoking and MSC V55 were independent predictors (male vs. female : OR=0.152, 95%CI=0.037-0.642, P0.001 ; smoking vs. non-smoking: OR=4.028, 95%CI=2.145-32.079, P=0.032 ; MSC-V55 : OR=2.665, 95%CI=1.172-3.365, P0.004). The cutoff of MSC-V55 was 10.38%, area under curve was 0.697, with sensitivity and specificity of 0.635 and 0.704, respectively. ConclusionsWe recommend MSC as a more reasonable method for oral mucosa contouring in TOMO treatment plan for nasopharyngeal carcinoma patients. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.