Intensity-modulated Radiotherapy Era Research Articles

Epidermal growth factor receptor‑targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real-world study.

Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7-55.9) months. The study group was associated with improved OS (hazard ratio [HR]=0.75, 95% CI: 0.57-0.99, p=0.038) and progression-free survival (PFS) (HR=0.74, 95% CI: 0.58-0.96, p=0.021). Subgroup analysis revealed that aged 50-60 year, IV, N2, radiotherapy dose≥60Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.

The effect of incidental dose to pelvic nodes in bladder-only irradiation in the era of IMRT: adosimetric study.

While three-dimensional radiotherapy (RT) causes high incidental nodal doses in bladder-only irradiation for muscle-invasive bladder cancer (MIBC), the impact on pelvic lymphatics is unclear in the era of intensity-modulated RT (IMRT). This study evaluates incidental doses to pelvic lymphatics in MIBC patients treated with IMRT. The data of 40MIBC patients treated with bladder-only IMRT and concurrent chemotherapy were retrospectively evaluated. The pelvic lymphatics were contoured on initial simulation images and incidental nodal doses were evaluated. The Statistical Package for the Social Sciences (SPSS) version23.0 (IBM, Armonk, NY, USA) was used for statistics. Median RT dose to the bladder was 60 Gy in 30fractions. In dosimetric analysis, median values of mean dose (Dmean) of the obturator, presacral, external iliac, internal iliac, and distal common iliac lymphatics were 33 Gy (range 4-50 Gy), 3 Gy (range 1-28 Gy), 9.5 Gy (range 3-41 Gy), 7.5 Gy (range 2-14 Gy), and 1 Gy (range 0-15 Gy), respectively. The Dmean of the obturator lymphatics was significantly higher (p < 0.001) and the Dmean of the distal common iliac lymphatics was significantly lower (p < 0.001) than all remaining lymphatic stations. The Dmean of the external iliac lymphatics was significantly higher than that of the presacral lymphatics (p < 0.001), but the difference with the internal iliac lymphatics was not statistically significant (p = 0.563). The incidental nodal doses with bladder-only IMRT are heterogeneous and remain below the generally accepted doses for microscopic disease eradication for bladder cancer.

Deletion of concurrent chemotherapy on the basis of sequential chemoradiotherapy for non-metastatic stage T4 nasopharyngeal carcinoma in IMRT era.

Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.

The potential overdose of heart and left anterior descending coronary artery region during intensity-modulated radiation therapy in patients with esophageal cancer.

This study aimed to investigate the changes in dose distribution in the heart and left anterior descending coronary artery region (LADR) during intensity-modulated radiation therapy (IMRT) in patients with esophageal cancer (EC) treated at our institution. The heart and LADR were delineated on the initial and off-cord boost planning computed tomography (CT) images. Cardiac volume reduction (CVR) was defined as the reduction in cardiac volume between the initial CT and off-cord boost CT at the dose of 36Gy irradiated. The involved field IMRT plan was created based on each initial and off-cord boost CT image and was analyzed based on the relationship between CVR and heart and LADR dose-volume parameters (Heart-Dmax, Heart-Dmean, Heart-V20, Heart-V30, Heart-V40, LADR-Dmax, LADR-Dmean, LADR-V15 and LADR-V30). Forty patients with EC were investigated between January 2016 and January 2022. The median CVR ratio during radiation therapy (RT) was 5.57% (range, -7.79 to 18.26%). Simple linear regression analysis revealed significant correlations between CVR during RT and changes in the heart and LADR dose-volume parameters. Some patients (>10%) experienced severe changes in the heart and LADR dose distribution. In three cases with reduced heart volume and primary tumor mass, the changes in LADR-V15 and LADR-V30 showed outliers. In conclusion, CVR during RT correlated with an increase in the heart and LADR dose. When both CVR and tumor volume reduction are large, a potential overdose of LADR during RT should be noted in the IMRT era.

Significance of chemotherapy for older patients with nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A propensity score matching analysis

IntroductionThis study aimed to evaluate the survival and prognosis of older patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy using propensity score matching (PSM). Materials and MethodsWe enrolled 841 older patients with NPC aged 60 years and above without metastasis receiving IMRT alone or chemoradiotherapy from 2012 to 2019. The comorbidity was assessed by adult comorbidity evaluation (ACE-27). PSM (1:3 ratio) was conducted between the two treatment groups based on four clinical factors including age, T-stage, N-stage, and ACE-27. Differences in overall survival (OS) and cancer-specific survival (CSS) were analyzed by the Kaplan-Meier method and Cox proportional hazard model. ResultsA total of 841 patients with NPC were included in the study, there were 94 patients in the IMRT alone group and 747 patients in the chemoradiotherapy (CRT) group. After a 1:3 ratio PSM, 89 patients underwent IMRT alone and 223 patients underwent CRT. The baseline analysis showed an insignificant difference after PSM (P > 0.05). In multivariate analysis, we found that ACE-27 (≥2) was associated with worse five-year OS and CSS (HR = 1.994, 95%CI: 1.276–3.116, P = 0.002; HR = 1.849, 95%CI: 1164–2.935, P = 0.009, respectively). Chemotherapy was an independent prognosticator of better five-year OS and CSS (HR = 0.333, 95%CI: 0.213–0.552, P < 0.001; HR = 0.327, 95%CI: 0.204–0.524, P < 0.001, respectively). In terms of subgroup analysis, chemotherapy was a statistically beneficial predictor for stage III-IV patients (P < 0.05), but no significant difference in stage II patients (P > 0.05). About the adverse events, the incidence of hepatotoxicity (P = 0.002), neutropenia (P < 0.001), anemia (P < 0.001), and thrombocytopenia (P < 0.001) were significantly higher in the CRT group. DiscussionCombined modality therapy was associated with improved five-year OS and CSS in older adults with stage III-IV NPC, but was not associated with improved survival over IMRT alone in patients with stage II disease. Risk factors including T3–4 disease, positive lymph nodes, ACE-27 score ≥ 2, and IMRT alone were were associated with worse OS and CSS. There was a significantly higher incidence of hepatotoxicity and blood toxicity in the CRT group.

Delta-Radiomics Guides Adaptive De-Intensification after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma in the IMRT Era

In the setting of intensity-modulated radiotherapy (IMRT) and induction chemotherapy (IC), the benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma (LANPC). This study aimed to construct a delta-radiomics model for benefit prediction and patient selection for omitting concurrent chemotherapy. Between December 2009 and December 2015, a total of 718 patients with LANPC treated with IC+IMRT or IC+concurrent chemoradiotherapy (CCRT) were retrospectively enrolled and randomly assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from magnetic resonance images of pre-IC and post-IC. Interclass correlation coefficients and Pearson correlation coefficients were calculated to select robust radiomic features. After univariate Cox analysis, a delta-radiomics signature was built using the LASSO-Cox regression. A nomogram incorporating the delta-radiomics signature and clinical prognostic factors was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated by Kaplan-Meier methods. The primary outcome was overall survival (OS). The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. It yielded an area under the receiver operating characteristic curve (AUC) of 0.77 (95% confidence interval [CI] 0.71 to 0.82) for the training set and 0.71 (95% CI 0.61 to 0.81) for the validation set. The nomogram composed of the delta-radiomic signature, age, T category, N category, pre-treatment Epstein-Barr virus DNA, and treatment showed great calibration and discrimination performance with an AUC of 0.80 (95% CI 0.75 to 0.85) for the training set and 0.75 (95% CI 0.64 to 0.85) for the validation set. Risk stratification by the nomogram excluding the treatment variable resulted in two risk groups with distinct OS. Significant better outcomes were observed in the high-risk patients with IC+CCRT compared to those with IC+IMRT (5-year OS: 73.8% vs. 61.4% in the training set and 85.8% vs. 65.6% in the validation set; all log-rank p < 0.05), while comparable outcomes between IC+CCRT and IC+IMRT were shown for the low-risk patients (95.8% vs. 95.8% in the training set and 92.2% vs. 88.3% in the validation set; all log-rank p > 0.05). The delta-radiomics signature was identified as an independent indicator of LANPC. Integrating clinical predictors with the delta-radiomics signature, the radiomics-based nomogram could predict individual's survival outcomes and benefits from concurrent chemotherapy after IC for LANPC. Low-risk patients with LANPC determined by the nomogram may be potential candidates for omission of concurrent chemotherapy following IC in the IMRT era.

Radiation therapy for cT1-2 carcinoma of the palatine tonsil diagnosed via a simple tonsillectomy: Dosimetry and patterns of care in the IMRT era

ObjectiveSmall carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated. Patients and methodsA retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018. Patients who received curative-intent intensity modulated radiotherapy (IMRT) without additional surgery were included. Target volumes were reviewed, and cumulative incidences of local failure and severe late dysphagia were calculated. ResultsFrom 638 oropharyngeal patients, 91 were diagnosed via simple tonsillectomy. Definitive IMRT with no additional surgery to the primary site was utilized in 57, and three with gross residual disease were excluded, leaving 54 for analysis. Margins were negative in 13%, close (<5 mm) in 13%, microscopically positive in 61%, and not reported in 13%. Doses typically delivered to gross disease (68–70.2 Gy in 33–35 fx or 66 Gy/30 fx) were prescribed to the tonsil bed in 37 (69%). Sixteen patients (29%) received doses from 60 to 66 Gy (≤2 Gy/fx) and one received 50 Gy (2 Gy/fx). No local failures were observed. One late oropharyngeal soft tissue ulcer occurred, treated conservatively (grade 2). At five years, the cumulative incidence of severe late dysphagia was 17.4% (95% CI 6.1–28.8%). ConclusionSmall tonsil carcinomas diagnosed by simple tonsillectomy represent a niche subset with favorable oncologic outcomes. Regardless, radiation oncologists tend to deliver full-dose to the tonsil bed. The necessity of this routine could be questioned in the modern era.

The prognosis of gliomas with different molecular subtypes in the era of intensity-modulated radiation therapy (IMRT).

This study aimed to evaluate the prognosis of glioma patients with different molecular subtypes of who treated with intensity-modulated radiation therapy (IMRT). We collected 45 glioma patients treated in our hospital between January 2017 and December 2020. All enrolled patients received postoperative IMRT and were divided into two groups based on the Isocitrate dehydrogenase (IDH status). Overall survival (OS) and progression-free survival (PFS) were estimated retrospectively. The median follow-up was 22 months (range 2-108.5 months). The 1-year OS of IDH-mut group and ΙDH-wild group was similar (77.3% vs. 81.5%, p = 0.16). While the 1-year PFS of IDH-mut group was significantly higher than that in ΙDH-wild group (90.4% vs. 39.8%, p = 0.0051). Subgroup analysis revealed that the 1-year PFS of IDH-mut/1p/19q codeletion group and IDH-mut/1p/19q noncodeletion group was significantly higher than in IDH-wild type patients. For patients with IDH-mut/MGMT-methylation, the outcome was no significant difference in OS, but PFS was longer than other subtypes. This retrospective study showed that 1-year PFS of patients with IDH mutated was better than IDH-wild type patients. In subgroups analysis, the outcomes were shown that patients with IDH-mut/ 1p/19q codeletion and patients with IDH-mut/1p/19q noncodeletion had longer 1-year PFS than IDH-wild type patients, but the OS was similar between the subgroups. Patients with IDH-mut/MGMT-methylation had the best prognosis in the whole subgroups. However, these results still need further confirmation of large sample size, prospectively, randomized controlled trails.

Clinical treatment considerations in the intensity-modulated radiotherapy era for parotid lymph node metastasis in patients with nasopharyngeal carcinoma

PurposeNo specific irradiation guidelines have been proposed for parotid lymph node (PLN) metastasis in patients with nasopharyngeal carcinoma (NPC). This study aimed to explore the dose prescription and target delineation for PLN metastasis in patients with NPC. MethodsWith the NPC database from a big-data platform, 10,685 patients with primarily diagnosed, non-distant metastatic, histologically proven NPC and treated with intensity modulated radiotherapy (IMRT) at our center from 2008 to 2019 were reviewed and those with PLN metastasis were enrolled in this study. Dosimetry parameters were collected from the dose-volume histograms (DVH). The primary endpoint was overall survival (OS). Least absolute shrinkage and selection operator regression (LASSO) was operated for variable selection. Multivariate Cox regression analysis was applied to identify the independent prognostic factors. ResultsPLN metastases were identified in 275/10685 (2.5%) patients. Of 367 positive PLN, 199 were in superficial intra-parotid, followed by 70 in deep intra-parotid, 54 in subparotid and 44 in subcutaneous pre-auricular. Better survival outcome was observed in PLN-radical IMRT group, compared with PLN-sparing group. In 190 patients received PLN-radical IMRT, multivariate analysis revealed that D95% of level VIII > 55 Gy was an independent beneficial prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and parotid relapse-free survival (PRFS). ConclusionBased on the distribution pattern of PLN metastasis in NPC and the result of dose-finding study, involving the ipsilateral level VIII into low-risk clinical target volume (CTV2) is recommended for NPC with PLN metastasis.

Nimotuzumab in combination with intensity modulated radiotherapy improve survival in locally advanced head and neck squamous cell carcinoma (LA-HNSCC): A multicenter-based real-world study.

e18006 Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by the high expression of epidermal growth factor receptor (EGFR). Randomized study has demonstrated a survival advantage associated with the use of EGFR antibody (C225) in conjunction with radiation in locally advanced HNSCC (LA-HNSCC). However, the role of EGFR antibody plus concurrent chemoradiotherapy (CCRT), especially in the intensity-modulated radiotherapy (IMRT) era, is still controversial. Therefore, we conducted a multicenter, retrospective real-world study to investigate whether adding nimotuzumab, a humanized EGFR antibody, to IMRT-based treatment could improve survival in LA-HNSCC (NCT04949503). Methods: All HNSCC patients treated between January 2015 and December 2018 from 8 hospitals in China were screened. Eventually, patients who completed at least 5 course of nimotuzumab were identified as study group and those who did not receive nimotuzumab were considered controlled group. Propensity score matching (PSM) was utilized to balance known confounding factors, such as clinical stage (AJCC 7 ed.), primary location, and so on. Overall survival (OS) and progression-free survival (PFS) were compared between two groups. The Log-rank test was rendered to examine the overall difference of two survival curves and the Cloglog transformation test was performed to compare two survivals at a fixed timepoint. Results: A total of 25442 patients were screened, 1931 patients were eligible and 612 patients (306 patients in each group) were matched by PSM for final analysis. The percentage of stage IV disease was approximate 80% in both groups, and the use of CCRT was 62.4% in study group and 65.4% in controlled group. Totally 250 (81.7%) patients received IMRT in study group and 275 (89.8%) patients received IMRT in controlled group. The follow up was cut off on Jan 19, 2023 and the median follow up time was 54.2 (95%CI: 52.7-55.9) months. Among the entire cohort, the addition of nimotuzumab was associated with improved OS (HR = 0.75, 95% CI: 0.57-0.99, Log rank p = 0.038; 3y-OS: 74.6% vs 63.3%, Cloglog p = 0.004) as well as significantly advantageous PFS (HR = 0.74, 95% CI: 0.58-0.96, Log rank p = 0.020; 3y-PFS: 57.7% vs 44.3%, Cloglog p = 0.009). Subgroup analysis revealed that stage IV, T1, N2, radiotherapy duration ≥ 6 weeks, without previous surgery and CCRT sub-cohort could gained more OS benefit from the addition of nimotuzumab. Beneficial subgroup for PFS included stage IV, T2, N2, radiotherapy duration ≥ 6 weeks, without previous surgery and CCRT sub-cohort. Conclusions: The addition of nimotuzumab to IMRT-incorporated treatment may provide both OS and PFS benefit for LA-HNSCC, in particular those with stage IV or N2 diseases, without previous surgery, receiving radiotherapy ≥ 6 weeks and CCRT. Clinical trial information: NCT04949503 .

Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy.

This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test. There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT. Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

T1-2N1M0 nasopharyngeal carcinoma chemotherapy or not: A retrospective study.

Radiotherapy (RT) combined with chemotherapy is the standard treatment for T1-2N1M0 nasopharyngeal carcinoma (NPC) based on conventional radiotherapy. However, intensity-modulated radiotherapy (IMRT) has narrowed the treatment gap between RT and chemoradiotherapy. Thus, this retrospective study aimed to compare the efficacy of RT and chemoradiotherapy (RT-chemo) in treating T1-2N1M0 NPC in the IMRT era. From January 2008 to December 2016, 343 consecutive patients with T1-2N1M0 NPC in two cancer centers were included. All patients received RT or RT-chemo, chemotherapy including induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT), CCRT, or CCRT + adjuvant chemotherapy (AC). The number of patients who received RT, CCRT, IC + CCRT, and CCRT + AC was 114, 101, 89, and 39. The survival rates were analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariable analysis was performed to identify valuable prognostic factors. The median follow-up time for survivors was 93 (range: 55-144) months. The 5-year overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) for the RT-chemo and RT groups were 93.7%, 88.5%, 93.8%, 93.8% and 93.0%, 87.7%, 91.9%, 91.2%, respectively (P>0.05 for all outcomes). No significant survival differences were found between the two groups. The T1N1M0 or T2N1M0 subgroup analysis showed that treatment outcomes had no significant differences between the RT and RT-chemo groups. After adjusting for various factors, treatment mode was not identified as an independent prognostic factor for all survival rates. In this study, outcomes of T1-2N1M0 NPC patients treated by IMRT alone were comparable to chemoradiotherapy, supporting the omission or postponement of chemotherapy.

Rates of osteoradionecrosis in resected oral cavity cancer reconstructed with free tissue transfer in the intensity-modulated radiotherapy era.

Resected oral cavity carcinoma defects are often reconstructed with osteocutaneous or soft-tissue free flaps, but risk of osteoradionecrosis (ORN) is unknown. This retrospective study included oral cavity carcinoma treated with free-tissue reconstruction and postoperative IMRT between 2000 and 2019. Risk-regression assessed risk factors for grade ≥2 ORN. One hundred fifty-five patients (51% male, 28% current smokers, mean age 62 ± 11 years) were included. Median follow-up was 32.6months (range, 1.0-190.6). Thirty-eight (25%) patients had fibular free flap for mandibular reconstruction, whereas 117 (76%) had soft-tissue reconstruction. Grade ≥2 ORN occurred in 14 (9.0%) patients, at a median 9.8months (range, 2.4-61.5) after IMRT. Post-radiation teeth extraction was significantly associated with ORN. One-year and 10-year ORN rates were 5.2% and 10%, respectively. ORN risk was comparable between osteocutaneous and soft-tissue reconstruction for resected oral cavity carcinoma. Osteocutaneous flaps can be safely performed with no excess concern for mandibular ORN.

74MO Clinical outcomes for pelvic node-positive vulvar carcinoma in the PET and IMRT era: Reassessing the stage IVb designation

Pelvic node-positive (PNP) vulvar carcinoma has historically had poor outcomes; 2-year DFS was 27% in GOG 37. Studies in this cohort were performed prior to widespread PET staging and intensity modulated radiotherapy (IMRT). We assessed clinical outcomes and prognostic factors in FIGO IVb patients in the PET and IMRT era, hypothesizing that PET staging and IMRT treatment may improve outcomes. Following IRB approval, we reviewed all patients with PNP vulvar squamous cell carcinoma (SCC) who received IMRT from 2012-2022. Patients treated palliatively were excluded. Eligible patients met stage IVb criteria and received simultaneous integrated boost (SIB) to radiologically positive lymph nodes (LN). Tumor size, grade, PET primary and LN SUVmax, largest LN size, LN anatomic location, p16 status, chemotherapy (CHT), and RT completion were recorded, as were survival (OS), disease free survival (DFS), local (LRFS)/regional (RRFS) recurrence and distant metastasis (DMFS). Patterns of recurrence and survival were examined via Kaplan Meier, with univariate analysis (UVA) via log-rank t-test. Multivariate analysis (MVA) was performed via Cox regression. 198 patients received RT for vulvar SCC, and 31 met inclusion criteria. Median follow up was 26 months (IQR 9-49) for patients completing RT (n=25) and 3 months (IQR 1-9) for patients not completing RT (n=6). 93.5% (n=29) had PET staging, with avid LN at external iliac (74.2%, n=23), common iliac (16.1%, n=5) and para-aortic (9.7%, n=3) echelons. RT was majority definitive/neoadjuvant (83.9%, n=26); 93.5% (n=29) received concurrent CHT. 22.5% (n=7) underwent LN dissection, with median 3 LN resected and 2 LN positive. With RT completion, 3-year OS and DFS were 64.1% and 69.6%, with 82.6% LRFS, 83.1% RRFS, and 77.5% DMFS. On UVA, LN SUVmax correlated with worse DFS, RRFS, and DMFS, and p16- status with worse OS, RRFS, and DMFS (p<0.05). LN SUVmax retained significance for DFS (p=0.045) and DMFS (p=0.041) on MVA. Clinical outcomes for PNP vulvar SCC have substantially improved in the PET and IMRT era, challenging the FIGO IVb designation. PET LN SUVmax may help predict patients at higher risk of DM, and p16+ status those with more favorable outcomes.

Survival effect of pre-RT PET-CT on cervical cancer: Image-guided intensity-modulated radiation therapy era.

No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). This is the first head-to-head propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT.

Nasopharyngeal carcinoma in a non-endemic country—Validation of the new NPC staging system

BackgroundNasopharyngeal carcinoma (NPC) staging has recently been updated, with the eighth edition of the AJCC/UICC. In the last ten years, Intensity Modulated Radiotherapy (IMRT) has become a standard treatment for NPC. The authors aim to assess the benefits of the new AJCC staging system in predicting prognosis, as well as the improvement in survival outcomes in the IMRT era, in non-edemic population. MethodsRetrospective study selecting patients treated for NPC between January 2009 and December 2019 in a cancer treatment center in Portugal. Initial TNM staging (according to the seventh edition of the AJCC/UICC) was collected and each patient was restaged according to the new TNM staging system. Overall survival (OS) and Distant Metastasis Free Survival (DMFS) stratified by T and N classification and stage (according to the both TNM staging systems) were analyzed. Univariate and multivariate analysis was performed to evaluate which factors influence OS and DMFS. Data in this series was compared with a previous report from the same institution, before IMRT standard use. Results113 patients were included, averaging 53.74 (±1.4) years old. With the new TNM staging, 5 patients were downstaged and 3 patients were upstaged. Over a median follow-up time of 41 months, the 5-year OS and DMFS were 77% and 79.8%, respectively. Neither the seventh nor the eighth editions of the AJCC/UICC staging system had good overall discrimination between each T classification OS and DMFS curves. Both the seventh and the eighth editions of the AJCC/UICC staging system had statistically significant overall discrimination between each N group and each stage group classification OS curves. Only N classification predicted OS in multivariate analysis. When comparing to a previous report from the same institution, OS has not improved majorly, especially in locoregionally advanced disease. ConclusionsTNM staging still presents limitations in adequately predicting OS and DMFS.

Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

The prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes in these patients. we identified patients with esophageal squamous cell carcinoma who were staged as ypT3/T4 and/or ypN+ after being treated with neoadjuvant chemoradiotherapy followed by esophagectomy between the years 2013 and 2019. Patients were divided into two groups based on whether they received adjuvant chemoradiotherapy. The Kaplan-Meier method and Cox regression modeling were performed for survival analyses and multivariable analysis, respectively. 76 eligible patients were included in the analyses. The median follow-up for the study cohort was 43.4 months. On Kaplan-Meier analyses of the overall population, adjuvant chemoradiotherapy was associated with significantly improved median overall survival (31.7 months vs. 16.3 months, p = 0.036). On Kaplan-Meier analyses of the 35 matched pairs generated by propensity score matching, adjuvant chemoradiotherapy was associated with significantly longer median overall survival (31.7 months vs. 14.3 months; p = 0.004) and median recurrence-free survival (18.9 months vs. 11.7 months; p = 0.020). In multivariable analysis, adjuvant chemoradiotherapy was independently associated with a 60% reduction in mortality (p = 0.003) and a 48% reduction in risk of recurrence (p = 0.035) after adjusting for putative confounders. In addition, microscopic positive resection margin and Mandard tumor regression grade 3-4 were independently associated with increased mortality and risk of recurrence. While a greater number of lymph nodes dissected was independently associated with significantly improved overall survival, the number of positive lymph nodes was independently associated with significantly worse overall survival and a trend (p = 0.058) towards worse recurrence-free survival. This study demonstrated that adjuvant CRT was independently associated with a significantly improved survival and lower risk of recurrence than observation in esophageal squamous cell carcinoma patients staged as ypT3 and/or ypN+ after receiving neoadjuvant chemoradiotherapy and radical surgery. The results of this study have implications for the design of future clinical trials and may improve treatment outcomes of patients in this setting who cannot afford or are without access to adjuvant nivolumab.

Prognostic values of the gross volume of metastatic lymph nodes in patients with esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy.

We aim to explore whether the gross volume of metastatic lymph nodes (GTVnd) and the gross volume of primary tumor (GTVp) could be prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT). We retrospectively analyzed 252 ESCC patients treated with dCCRT in the eraofintensity-modulatedradiation therapy (IMRT) at our institution. The cut-off value for the GTVnd derived from the restricted cubic splines (RCS) was determined. Univariate and multivariate Cox proportional hazard models were performed to determine the association between GTVnd and prognosis. we performed recursive partitioning analysis (RPA) method using GTVnd to develop a new risk stratification (TGTVndM). Moreover, the linear trend χ2, likelihood ratio χ2, and akaike information criterion (AIC) were used to determine the prognostic value between the TNM and TGTVndM staging systems. The five-year overall survival (OS) rate was 30.6%, with a median follow-up of 38 months. The cut-off value of GTVnd determined by the RCS was 4.35 cm3. GTVnd≥4.35 cm3 was an independent and significant negative prognostic factor for OS (HR=1.949, P<0.001), progression free survival (PFS) (HR=1.425, P=0.048), and distance metastasis free survival (DMFS) (HR=2.548, P=0.001). In multivariable analysis, gender, clinical T stage, and GTVnd were independently associated with OS. RPA segregated patients into 3 prognostic groups: high risk (T1-4 GTVnd≥4.35, n=126, III stage), intermediate risk (T4 GTVnd<4.35,n=38,II stage), and low risk(T1-3GTVnd<4.35, n=88, I stage). The 5-year OS(P<0.001), PFS (P=0.002), and DMFS (P=0.001) were significantly worse in high-risk group in comparison with the intermediate and low risk groups. Compared with the TNM staging system, the clinical T stage combined with GTVnd (TGTVndM) had a higher linear trend χ2 (26.38 versus 25.77), higher likelihood ratio χ2 (24.39 versus 20.69), and lower AIC (1255.07 versus 1260.06). GTVnd may serve as a good prognostic factor in predicting distant metastasis and death for ESCC patients treated with dCCRT. The TGTVndM staging system demonstrated superior accuracy for predicting OS and could serve as a more effective prognostic guidance for unresectable ESCC patients.

Hypofractionated versus conventional intensity-modulated radiation irradiation (HARVEST-adjuvant): study protocol for a randomised non-inferior multicentre phase III trial

IntroductionShort course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40–42.5 Gy in 15–16 fractions has...

Adult Head and Neck Rhabdomyosarcoma: Management, Outcomes, and the Effect of Intensity Modulated Radiation Therapy on Locoregional Control

PurposeOnly 9% of adult rhabdomyosarcomas (RMS) present with primary disease in the head and neck (HNRMS). Management is often extrapolated from the pediatric experience in which prognosis is better but treatment imperatives differ. We report management and outcomes of adult HNRMS treated over 3 decades. Methods and MaterialsAdult HNRMS treated from 1984 to 2017 were reviewed. HNRMS were categorized as embryonal/alveolar (E/A) or pleomorphic (P). Standard management was as follows: E/A-HNRMS were treated with neoadjuvant chemotherapy, definitive chemoradiotherapy (CRT), and then maintenance chemotherapy. P-HNRMS were generally treated with surgery +/– radiation. Intensity modulated radiation therapy (IMRT) was adopted from 2005 onward. ResultsFifty-eight patients were eligible; the median age was 32 years. Seventy-six percent of tumors (n = 45) were parameningeal and 45% (n = 26) were >5 cm. Of 45 patients with M0 HNRMS treated with curative intent, 33 (73%) were E/A-HNRMS and 12 (27%) P-HNRMS. Patients with E/A-HNRMS received definitive RT with 66 to 70 Gy in 2 Gy per fraction. Elective nodal RT was routinely delivered. In the pre-IMRT era (before 2005), 12 of 23 (52%) patients with M0 E/A-HNRMS experienced locoregional recurrences. In the IMRT era (2005 and onward), 1 of 10 patients (10%) with M0 disease recurred locally; this patient achieved a complete clinical response despite a 3-week interruption after 48 Gy because of local toxicity but experienced an in-field local recurrence 45 months later that resulted in death. Locoregional control was superior in the IMRT era vs pre-IMRT era (P = .049). Distant metastasis among patients with E/A-HNRMS was the predominant mode of treatment failure (n = 17 of 33, 52%). ConclusionsOur study shows a high rate of locoregional control for adult E/A-HNRMS following definitive CRT using IMRT, and CRT should be considered for the majority of patients in this population. In contrast, P-HNRMS is distinct and requires surgery +/– RT.