Definitive Radiotherapy In Patients Research Articles

Laryngeal Preservation Rate and Salvage Therapy Following Initial Recurrence in a Real-world Setting After Definitive Radiation Therapy in Patients With Locally Advanced Laryngeal Squamous Cell Carcinoma.

The larynx plays a pivotal role in vocalization and airway protection, and laryngeal cancer manifests through various symptoms. Contemporary strategies focus on laryngeal preservation, particularly through non-surgical modality therapies that utilize radiotherapy. The aim of this study was to assess the laryngeal preservation rate after definitive radiation therapy in patients with locally advanced laryngeal squamous cell carcinoma and investigate salvage therapy subsequent to the initial recurrence in a real-world context. Analysis included a total of 40 patients with locally advanced laryngeal squamous cell carcinoma who were treated with definitive radiotherapy in the University of Tokyo Hospital. Treatment involved external beam radiotherapy (70 Gy in 35 fractions) with elective nodal irradiation. The main study outcomes were assessment of survival, overall survival, local control, and the factors influencing laryngeal preservation. The patients exhibited a median age of 64.5 years, and 80% of them were men. Chemotherapy was administered to 82.5% of the patients. The 3-year overall survival, progression-free, and laryngeal preservation survival rates were 86.3%, 66.8%, and 78.4%, respectively. Univariate and multivariate analyses identified chemotherapy to be significantly associated with favorable laryngeal preservation survival (p<0.001). Definitive radiotherapy results in favorable outcomes for laryngeal preservation in locally advanced laryngeal squamous cell carcinoma. This study emphasizes the importance of chemotherapy in comprehensive patient management. Nevertheless, larger prospective studies are crucial to validate and optimize therapeutic approaches for this condition.

Proposals for the delineation of neck clinical target volume for definitive Radiation therapy in patients with oral/ oropharyngeal squamous cell cancer based on lymph node distribution

Purpose/Objective(s)To establish the distribution pattern of cervical lymph node metastasis (LNM) and propose optimized clinical target volume (CTV) boundaries specific to oral/ oropharyngeal squamous cell cancer (OSCC/OPSCC). Materials/Methods531 patients with pathologically confirmed OSCC/OPSCC were enrolled from January 2013 to June 2022. Patients were stratified into two groups based on the minimal distance from the lesion's edge to the body's midline: ≤1 cm or > 1 cm. The geometric center of cervical metastatic LN was marked on a template CT. LN distribution probability maps were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for CTV boundaries specific to OSCC/OPSCC. ResultsA total of 1962 positive LNs were enrolled. Compared with the > 1 cm group, the ≤ 1 cm group has following feature tendencies: male smokers, younger, median organs, large gross lesion, infiltrative growth pattern, contralateral LNM. The most frequently involved level of LNM was ipsilateral II, but ipsilateral Ib had the highest involvement rate in the > 1 cm OSCC group. In addition, tongue cancer had a higher incidence of LN extranodal extension (ENE), which mainly distributes in ipsilateral level II. The skip metastasis was prone to from level III to Vb (3.5 %) in LN(+)/ENE (-), and level Ib to VIa (3.7 %) in LN(+)/ENE (+). Accordingly, we proposed the following modifications: 1. only including lateral and posterior margin of submandibular gland within 5 mm; 2. retracting posterior boundary of level II to front edge of levator scapula muscle, and descending the upper boundary to transverse process of C2 vertebra only for OSCC; 3. including posterior third of thyroglossal muscle or anterior edge of sternocleidomastoid muscle; 4. sparing level Va in case of only level II involvement; 5. including upper area of the thyroid cartilage plate in case of level Ib LN(+)/ENE (+); 6. sparing level VIIa is considered. ConclusionThis is the first description of LN topographic spread patterns for OSCC/OPSCC. Modified CTV for prophylactic irradiation was proposed to spare the organs at risk and minimize adverse effects.

Indian clinical practice consensus guidelines for the management of oral cavity cancer: Update 2022

The treatment of oral cavity cancer primarily depends on the location, tumor size, and feasibility of organ preservation in patients with negative margins. A liquid biopsy is a minimally invasive approach for detecting blood-based signatures such as circulating tumor cells (CTCs) and circulatory tumor DNA (ctDNA). To assess the presence of occult metastatic disease, sentinel lymph node biopsy (SLNB) is recommended in early-stage oral cavity cancer (OCC). In India, surgery is the preferred choice of treatment for oral cancers. Selected patients, who are medically inoperable or refuse surgery, should be given definitive radiotherapy (RT) as an alternative to surgery. Concurrent chemoradiation (CCRT) may be considered an alternative option to definitive RT in patients with unresectable oral cancer.

Long-term clinical outcomes and prognosis after definitive radiotherapy for patients with cervical esophageal squamous cell carcinoma: a single-institution retrospective study.

Definitive radiotherapy has become a more common treatment for cervical esophageal squamous cell carcinoma (CESCC), but data about long-term clinical outcomes is still relatively sparse. The purpose of this study was to describe long-term clinical outcomes after definitive radiotherapy for CESCC, and identify the prognostic factors influencing these outcomes. We retrospectively analyzed all patients who received definitive radiotherapy for CESCC at our institution between 2006 and 2014. The overall survival (OS) rate, locoregional failure-free survival (LRFFS) rate, and toxicities were retrospectively evaluated during long-term follow-up. Univariate and multivariate analyses were performed to identify prognostic factors. A total of 120 patients were included for analysis. The median prescribed radiation dose for the gross tumor and metastatic lymph nodes was 60 Gy. Elective nodal irradiation (ENI) was performed on 99 patients (83%); 90 patients (75%) received concurrent chemotherapy. The OS rates were 22.7% at 5 years and 14.9% at 8 years. The LRFFS rates at 3, 5, and 8 years were 27.5%, 21.7%, and 15.0%, respectively. The univariate analysis suggested that N classification and non-regional lymph node metastasis (M1Lym) status were independent risk factors for overall survival (P<0.01). A dose of more than 60 Gy didn't have a statistically significant influence in the multivariate analysis, although a total dose of more than 60 Gy was associated with improved survival in the univariate analysis. Concurrent chemotherapy was not associated with OS or LRFFS time in the univariate or multivariate analysis. A total of 74 patients (61.7%) experienced locoregional treatment failure. The most commonly documented acute toxicities were grade 1 and grade 2 toxicities in 61 patients (50.8%). There were 2 patients diagnosed with hypothyroidism as a late toxicity event. Definitive radiotherapy is a reasonable curative treatment option with laryngopharyngeal preservation for CESCC patients. Radical treatments for lymph node metastases may improve the OS and LRFFS times. Monitoring for thyroid function may be warranted during long-term follow-up.

Definitive radiotherapy in patients with clinical T1N0M0 esophageal squamous cell carcinoma: A multicenter retrospective study (KROG 21–10)

PurposeTo assess the failure pattern and analyze the treatment scheme of definitive radiation therapy (RT) for T1N0M0 esophageal squamous cell carcinoma (ESCC). MethodsWe performed a multi-institutional retrospective analysis in T1N0M0 ESCC patients who underwent definitive RT from 2010 to 2019. Patterns of failure were demonstrated as in-, and out-field locoregional, and distant metastasis. In the analysis, freedom-from locoregional recurrence (FFLRR) and their association with clinicopathologic factors were evaluated. Propensity score matching in cT1b patients was done. Results168 patients were included with a median follow-up of 34.0 months, and 26 cT1a, 116 cT1b disease. The rates of 3-year all and locoregional recurrence for cT1a were 30.5% and 24.1% and those for cT1b were 27.1% and 25.9%, respectively. Among 116 cT1b patients, 69 patients received elective nodal irradiation (ENI) and 47 received involved field irradiation (IFI). After propensity score matching, the 3-year FFLRR rate was 84.5%. There was no difference between ENI and IFI in FFLRR (P = 0.831) and OS (P = 0.525). The 3-year FFLRR was 83.8% (95% Confidence interval (CI), 61.8–93.8%) in IFI group and 85.3% (95% CI, 65.1–94.3%) in ENI group. In multivariate analysis, concurrent chemotherapy use was marginally associated with FFLRR (Hazard ratio, 0.16; P = 0.064). ConclusioncT1a patients who cannot receive endoscopic resection showed similar failure rates as cT1b patients, questioning the staging accuracy and raised the need for thorough treatment like chemoradiotherapy. In cT1b patients, IFI with 50 to 60 Gy and concurrent chemotherapy could be reasonable.

Definitive Radiotherapy in Patients with Clinical T1N0M0 Esophageal Squamous Cell Carcinoma: A Multicenter Retrospective Study

In this study, we aimed to assess the failure pattern and survival outcomes and to analyze the optimal treatment field of definitive RT for T1N0M0 esophageal squamous cell carcinoma (ESCC). We performed a retrospective analysis in a multi-institutional cohort of patients with histologically confirmed T1N0M0 ESCC. We included patients who underwent RT with definitive aim from 2010 to 2019. Patterns of failure were demonstrated as in-field locoregional, out-field locoregional and distant metastasis. In the survival analysis, freedom from locoregional recurrence and their association with clinicopathologic risk factors were analyzed. We performed a propensity score matching in the cT1b patients to adjust for the heterogeneity of radiation technique, radiation dose and the use of concurrent chemotherapy. A total of 168 patients were included with a median follow-up of 34.0 months, and there were 20 cT1a, 94 cT1b and 24 cT1x, (cT1, not otherwise specified) patients. The rates of all and locoregional failure were 26.9% and 23.1% for cT1a and 25.0% and 22.4% for cT1b patients. 10 (10.6%) patients experienced grade ≥ 3 adverse events. Among 116 cT1b patients, 69 patients received elective nodal irradiation (ENI) and 47 patients received involved field irradiation (IFI). After propensity score matching, the 3-year FFLRR rate was 84.5% (95% Confidence Interval, 71.0 - 92.1%). There was no significant difference between the ENI and IFI patients in FFLRR (Log-rank P = 0.831). In the multivariate analysis, the use of concurrent chemotherapy was the only factor marginally associated with FFLRR (Hazard ratio, 0.17; 95% CI, 0.02 - 1.13; P = 0.067). cT1a patients who cannot receive endoscopic resection, showed similar rates of failure compared with cT1b patients, which questioned the accuracy of the staging and raised the need for through treatment such as chemoradiotherapy. In cT1b patients, IFI using dose of 50 to 60 Gy with concurrent chemotherapy could be a reasonable treatment option.

PO-1471 PSMA-PET-based Definitive Radiotherapy for Patients with Prostate Cancer - Outcome and Feasibility

PO-1471 PSMA-PET-based Definitive Radiotherapy for Patients with Prostate Cancer - Outcome and Feasibility

CD8-positive Tumor-infiltrating Lymphocytes and Prognosis in Radiotherapy for Uterine Cervical Squamous Cell Carcinoma.

Prognostic factors, including CD8-positive tumor-infiltrating lymphocytes (CD8+TILs), in definitive radiotherapy (RT) for squamous cell carcinoma (SqCC) of the uterine cervix need to be studied. This study aimed to explore these factors in a retrospective cohort. Patients with SqCC who underwent definitive RT comprising external beam RT and intracavitary brachytherapy at our facility between April 2006 and November 2013 were evaluated. CD8 immunohistochemistry was performed in pre-treatment biopsy samples to analyze the prognostic significance of CD8+TILs in the tumor nest. Positive staining was defined as at least one CD8+ lymphocyte infiltrating the tumor area in the specimen. In total, 150 consecutive patients were included. Among them, 66 (43.7%) patients had International Federation of Gynecology and Obstetrics (FIGO, 2008 edition) stage IIIA or higher progressive disease. The median follow-up period was 61 months. In the entire cohort, the 5-year cumulative rates of overall survival (OS), progression-free survival (PFS), and pelvic recurrence-free rate (PRFR) were 75.6%, 69.6%, and 84.8%, respectively. Of the 150 patients, 120 (80.0%) patients were CD8+TIL positive. The independent favorable prognostic factors were FIGO stage I or II disease, administration of concurrent chemotherapy, and CD8+TILs for OS (p=0.028, 0.005, and 0.038, respectively); FIGO stage I or II disease and CD8+TILs for PFS (p=0.015 and <0.001, respectively); and CD8+TILs for PRFR (p=0.017). The presence of CD8+TILs in the tumor nest may be a favorable prognostic factor of survival after definitive RT in patients with SqCC of the uterine cervix.

Predicting risk factors for hypothyroidism after definitive radiotherapy for early glottic carcinomas.

Hypothyroidism may occur after definitive radiotherapy in rare cases of early glottic carcinoma. However, to the best of our knowledge, no study to date has examined the risk factors for hypothyroidism specifically after definitive radiotherapy in patients with early glottic carcinoma. The present study determined risk factors for hypothyroidism after definitive radiotherapy in patients with early glottic carcinoma. This was a retrospective study that included 73 patients with T1 or T2, N0 glottic squamous cell carcinoma who underwent radiotherapy between June 3, 2009 and December 25, 2020. Demographic and clinical characteristics, including age, sex, tumor stage and pretreatment thyroid volume, were examined to elucidate the clinical risk factors for hypothyroidism. Field size, total prescribed dose and thyroid receiving dose were evaluated as dosimetric risk factors for hypothyroidism. Irradiated underlying thyroid volumes of more than 5, 10, 20, 30, 40, 50, 60 and 65 Gy (V5Gy, V10Gy, V20Gy, V30Gy, V40Gy, V50Gy, V60Gy and V65Gy) and mean thyroid dose were included as thyroid receiving doses. The median follow-up duration was 61 months (range, 7-150 months). Hypothyroidism was present in 15 (21%) of the 73 patients, including 12 and 3 patients with grade 1 and 2 hypothyroidism, respectively. Among the demographic and clinical factors, sex and pretreatment thyroid volume were significantly associated with hypothyroidism (P=0.007 and P<0.001, respectively). Among the dosimetric factors, the presence of hypothyroidism was significantly associated with V5Gy (P=0.012), V10Gy (P=0.015), V20Gy (P=0.020), V30Gy (P=0.024), V40Gy (P=0.028), V50Gy (P=0.028), V60Gy (P=0.027) and mean thyroid dose (P=0.023). In conclusion, sex, pretreatment thyroid volume and thyroid receiving dose were associated with hypothyroidism after definitive radiotherapy in patients with early glottic carcinoma. Particularly, the receiving dose to the thyroid gland should be reduced in female patients and in those with small thyroid volumes who are at higher risk for hypothyroidism following radiotherapy.

Prognostic Value of Change in Albumin and Body Mass Index during and after Definitive Radiotherapy in Patients with Locally Advanced Cervical Cancer

<h3>Purpose/Objective(s)</h3> Definitive radiotherapy (RT) is the standard treatment in patients with locally advanced cervical cancer (LACC). Many studies have shown that in addition to the intrinsic characteristics of the tumor, there are many other factors can also affect the prognosis, such as baseline nutritional and inflammation status. However, which of these factors, or their alterations during radiotherapy, has a greater impact on prognosis is unclear on survival is unknown. Therefore, the purpose of this study was to observe changes in these factors during RT and to evaluate the prognostic impact of these factors and their changes in clinical practice. <h3>Materials/Methods</h3> A total of 229 patients were involved in this retrospective study. All patients received definitive RT at a single institution. Clinical pathological characteristics and eight inflammatory and nutritional factors (albumin, weight, Body Mass Index (BMI), neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, etc.) of patients were collected at pre-, during and post-radiation. Changes in those parameters at different radiotherapy periods were evaluated, and the association between those parameters and their changes with progression-free survival (PFS) and overall survival (OS) were assessed at 3 years. <h3>Results</h3> The median follow-up periods were 42.3 months for all patients. During RT, almost all the parameters reduced significantly, and after RT, albumin levels returned to pre-treatment levels, but the body weight was further significantly reduced compare with that during RT (p < 0.001). In univariate analysis, neither baseline nutritional nor inflammatory factor levels were shown to be associated with prognosis, whereas changes in albumin and body weight during RT were associated with prognosis. In multivariate analysis, non-SCC (HR 2.747 for PFS, <i>p</i> =0.016; HR 2.983 for OS, p=0.016), a decrease >0.2kg/m² in BMI during and post RT (HR 2.595 for PFS, <i>p</i> <0.001; HR 2.579 for OS, <i>p</i> =0.002), and albumin <35g/L (defined as hypoalbuminemia) during RT (HR 2.208 for PFS, <i>p</i> =0.004; HR 2.069 for OS, <i>p</i> =0.021), were independent predictors of poor prognosis for both PFS and OS, ranking with gradually decreased hazard ratios. Hypoalbuminemia during RT was more common in patients with older age, lower baseline hemoglobin and albumin levels, BMI <25kg/m², concurrent chemotherapy with weekly cisplatin and higher incidence of diarrhea during treatment. However, the decrease in BMI during and post RT showed no significant association with patients' baseline characteristics. <h3>Conclusion</h3> Changes in albumin and BMI during or after RT showed more prognostic value than their baseline levels or other hematological and inflammatory parameters in LACC. Therefore, prevention of hypoalbuminemia during RT and maintenance of BMI in the middle and later stages of RT are the management priorities in the clinical practice of LACC.

Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.

The Outcomes of Definitive Radiotherapy in Patients with Prostate Cancer Using Simultaneous Integrated Boost Technique

<h3>Purpose/Objective(s)</h3> Previous studies had shown a dose-response relationship in prostate cancer during radiotherapy (RT). The clinical outcomes of prostate cancer patients treated with definitive RT using the simultaneous-integrated boost (SIB) technique were investigated in this study. <h3>Materials/Methods</h3> The clinical data of 556 prostate cancer patients who underwent RT using the SIB technique between September 2012 and September 2021 were retrospectively analyzed. In 39 fractions, patients received 78 Gy to the entire prostate±seminal vesicles and 86 Gy to the intraprostatic lesion (IPL). In addition, high-risk patients received 54 Gy pelvic field irradiation. Diffusion-weighted magnetic resonance imaging was used to define the IPL. Failure from biochemical failure (FFBF) and prostate-cancer specific survival (PCSS) were the primary endpoints. Secondary endpoints were progression free survival (PFS) and toxicity. <h3>Results</h3> The median age of the population was 69 years (range: 47–89 years). According to D'Amico risk categories, there were 175 patients (31.5%) classified as low risk, 186 patients (33.4%) classified as intermediate risk, and 195 patients (35.1%) classified as high risk. 253 patients (54.5%) received androgen deprivation therapy. The median duration of follow-up was 58.2 months (range, 4.7–126.8 months) for the entire cohort. The 5-year FFBF, PCSS, and PFS rates were respectively 93.3%, 98.5%, and 84.1%. In 40 patients (7.2%), progression was observed as biochemical failure in 16 patients, distant metastasis in 2 patients, and both biochemical failure and distant metastasis in 22 patients. Only four patients (0.7%) had a local recurrence. Univariate analysis revealed that the pretreatment PSA value, T and N stages, ISUP score, and D'Amico risk groups were all significant prognostic factors for FFBF and PCSS. PSA levels higher than 20 ng/mL [HR=3.39 (95% CI, 1.28–8.94); p=0.01], nodal metastasis [HR=4.03 (95% CI, 1.61–10.03); p=0.003], high risk disease [HR=6.66 (95% CI, 1.72–25.77); p=0.001], and higher ISUP scores [HR=2.31 (95% CI, 1.53–3.49); p<0.001] were all independent predictors of worse FFBF. In multivariable analysis, the significant predictors of worse PCSS were high risk disease [HR=8.96 (95% CI: 2.13–19.71; p=0.01] and a higher ISUP score [HR=12.21 (95% CI: 1.70–87.74; p=0.004]. Acute gastrointestinal (GI) and genitourinary (GU) system toxicities of grade 2 or greater were observed in 7.4% and 14.0% of patients, respectively. Late GI and GU toxicities of grade 2 or greater were observed in 5.3% and 6.9% of patients, respectively. <h3>Conclusion</h3> The treatment strategy of 78 Gy delivered to the entire prostate with a boost dose of 86 Gy to IPL was effective and safe, with excellent biochemical control and PCSS, and very low toxicity rates. Longer follow-up and randomized trials are needed to validate our findings.

Disparities in the quality of definitive radiation therapy for patients with locally advanced cervical cancer (059)

<b>Objectives:</b> To examine disparities and patterns of definitive radiation therapy administration for patients with locally advanced cervical cancer (LACC) and their impact on overall survival. <b>Methods:</b> Black and non-Hispanic White (NHW) patients diagnosed between 2004 and 2015 with locally advanced cervical cancer (FIGO 2009 stage IB2-IVA), who had no history of another tumor, did not undergo hysterectomy, received external beam radiation therapy of at least 45 Gy, and had at least one month of follow-up, were identified in the National Cancer Database. We examined three quality metrics described in the National Comprehensive Cancer Network (NCCN) guidelines; utilization of radio-sensitizing chemotherapy (defined as chemotherapy administered within two weeks from radiotherapy initiation), receipt of brachytherapy, and completion of radiation treatment within eight weeks from initiation. Clinical-pathologic characteristics were compared with the Chi-square test. Overall survival was evaluated with Cox models after controlling for a priori selected confounders. <b>Results:</b> A total of 9940 patients with LACC were identified; 2242 (22.6%) were Black, and 7698 (77.4%) were NHW. Black patients were more likely to have squamous cell histology (91.3% vs 84.7%, p<0.001), medical comorbid conditions (17.1% vs 14.5%, p<0.001), government-issued insurance (55% vs 46.2%, p<0.001), and be managed at academic facilities (55.6% vs 42.3%, p<0.001). Stage distribution (49.5% vs 47.2% stage III-IVA, p=0.06) and patient age (median 52 years for both groups) were comparable between Black and NHW patients. However, Black patients were more likely to receive all treatment at the reporting facility (79.3% vs 71.7%, p<0.001) and reside within a short distance (<12.5 miles) from the treatment facility (69.3% vs 47.2%, p<0.001). In the present cohort, 5432 (54.6%) patients completed treatment within eight weeks, 8794 (88.5%) received radio-sensitizing chemotherapy, and 6453 (64.9%) received brachytherapy. All three-quality metrics were met for 2981 patients (30%). Black patients were less likely to have treatment that fulfilled all three-quality metrics (26% vs 31.2%, p<0.001) even after controlling for histology, age, insurance, comorbid conditions, and disease stage (OR: 0.82, 95% CI: 0.73-0.91). Patients who received guideline conformant radiation therapy had better OS after controlling for age, comorbid conditions, disease stage, histology, and insurance (HR: 0.67, 95% CI: 0.63-0.72). A survival advantage for patients receiving guideline conformant radiation therapy was present for both WNH (HR: 0.69; 95% CI: 0.64-0.75) and Black patients (HR: 0.60, 95% CI: 0.51-0.71). <b>Conclusions:</b> Approximately one in three patients with LACC received definitive radiotherapy that met all quality metrics and had superior outcomes even after controlling for confounders. Black patients were less likely to receive guideline conformant radiotherapy than WNH, even though they reside closer to treatment facilities and are more likely to present to academic institutions.

Quantifying the absolute benefit of neoadjuvant chemotherapy followed by definitive therapy in patients with muscle-invasive bladder cancer: A systematic review and meta-analysis.

4594 Background: Cisplatin based neoadjuvant chemotherapy (NAC) followed by definitive therapy improves survival in patients with muscle invasive bladder cancer (MIBC). However, the clinical benefit of NAC might vary with the choice of definitive therapy. Therefore, we assessed the absolute benefit of NAC followed by radical cystectomy or radical radiotherapy separately using the totality of evidence. Methods: MEDLINE and EMBASE were systematically searched to identify randomized trials assessing cisplatin based neoadjuvant chemotherapy followed by either radical cystectomy or definitive radiotherapy in patients with MIBC. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). Treatment effects were expressed as hazard ratios (HR) with 95% confidence interval (CI). Incidence rate ratios were calculated to estimate time to event outcomes for trials not reporting HR. A random-effects DerSimonian-Laird meta-analysis was conducted. Absolute effects were then obtained using baseline risks from the control arm of RCTs. Results: Of 4887 studies identified, 13 trials with 2529 patients were included in this meta-analysis. Most trials included patients with T2-4 and N0 patients and only 3 trials included patients with node positive disease. Total of 180 (47%) DFS events were observed with NAC+RC compared to 213 (56%) events in RC alone (HR: 0.72; 95% CI: 0.59-0.89) and 346 (58%) OS events were observed with NAC+ RC compared to 385 (52%) events in RC alone (HR: 0.80; 95% CI: 0.69-0.92). Total of 186 (70%) DFS events were observed with NAC + radiotherapy compared to 205 (71%) events in radiotherapy alone (HR: 0.91; 95% CI: 0.74-1.12) and 263 (58%) OS events were observed with NAC+ radiotherapy compared to 294 (61%) events in radiotherapy alone (HR:0.93; 95% CI: 0.79-1.08). Conclusions: The choice of definitive therapy after cisplatin-based NAC impacts survival in patients with MIBC. RC after NAC improved DFS (114 fewer events per 1000 events) and OS (76 fewer per 1000 events) whereas radiotherapy after NAC showed no survival benefit. [Table: see text]

Determining the suitability of definitive radiation therapy in patients with metastatic nasopharyngeal carcinoma based on PET/CT: a large cohort study.

To determine patients with de novo metastatic nasopharyngeal carcinoma (mNPC) who would benefit from receiving definitive radiation therapy (DRT) along with their pre-existing palliative chemotherapy (PCT) by evaluating their post-PCT Deauville scores and EBV DNA. A total of 570 mNPC patients, treated with PCT or PCT+DRT, were studied. EBV DNA levels, along with post-PCT Deauville scores, were used to stratify risk based on the recursive partitioning analysis (RPA). Significant differences were observed in the survival rates of patients with Deauville scores of 1-3 and 4-5 (2-year progression-free survival (PFS): 23.4% versus 8.5%, p < 0.001; 2-year overall survival (OS): 56.8% versus 18.8%, p < 0.001). RPA yielded three distinct groups in the increasing order of risk (Deauville scores of all RPA I-II were within the range of 1-3): (1) RPA I: EBV DNA levels at a pretreatment concentration ≤ 4000 copies/mL and undetectable post-PCT; (2) RPA II: EBV DNA levels either at a pretreatment concentration > 4000 copies/mL or at a pretreatment concentration ≤ 4000 copies/mL and detectable post-PCT; (3) RPA III: Deauville scores 4-5. While patients in RPA I and RPA II had significantly PFS rates when treated with PCT+DRT than when treated with PCT alone (RPA I: 72.7% versus 13.4%, RPA II: 37.8% versus 6.3%), those in RPA III did not experience such PFS benefits (6.5% versus 9.7%). PCT+DRT might improve the survival rates in mNPC patients in the low- and mid-risk strata but not those of patients in the high-risk strata. We use the Deauville scores and the concentrations of the Epstein-Barr virus (EBV) DNA to determine those patients with de novo metastatic NPC who would benefit from radiation therapy.

Early onset of severe lymphopenia during definitive radiotherapy correlates with mean body dose and predicts poor survival in cervical cancer.

BACKGROUND: Lymphopenia during definitive radiotherapy (RT) has been shown to reduce survival in patients with cervical cancer. However, there are few studies on the significance of onset time of lymphopenia during RT in patients with cervical cancer.OBJECTIVE: This study aimed to exam the prognostic significance of early onset of severe lymphopenia (EOSL) during definitive RT in patients with cervical cancer.METHODS: Newly diagnosed cervical cancer patients treated with definitive RT from January 2015 to December 2019 were eligible for this retrospective study. EOSL was defined as first onset of grade 3–4 lymphopenia 3 weeks from the start of RT. Mean body dose (MBD) was the mean radiation dose absorbed by the body during the whole course of external beam RT (EBRT) and was directly obtained from the dose volume histogram (DVH) of the EBRT planning. Logistic regression analysis and restricted cubic spline (RCS) models were applied to assess relationships between clinicopathological factors and EOSL. Survival analysis was performed using Kaplan-Meier curves and log-rank test. A COX regression model was developed to predict overall survival (OS).RESULTS: A total of 104 patients were included and 59.6% had EOSL. MBD ( 0.04), concurrent cisplatin ( 0.011), and pre-RT absolute lymphocyte count (ALC) ( 0.001) were associated with EOSL. A linear relationship ( for non-linearity 0.803) between MBD and risk of EOSL was found. Patients with EOSL had decreased OS (2-yr 75.1% vs 91.1%, 0.021) and progression-free survival (PFS) (2-yr 71.2% vs 83.7%, 0.071). An OS prediction COX model was developed with C-index of 0.835 and AUC of 0.872.CONCLUSIONS: EOSL during definitive RT correlates with MBD and predicts poor survival in patients with cervical cancer.

Supplementary for Prognostic value of change in albumin and BMI during and after definitive radiotherapy in patients with LACC

Supplementary for Prognostic value of change in albumin and BMI during and after definitive radiotherapy in patients with LACC

The importance of weight loss during definitive radiotherapy in patients with laryngeal carcinoma.

The aim of this study is to determine the prognostic significance of weight loss (WL) on overall survival (OS) and progression-free survival (PFS) in patients with locally advanced unresectable laryngeal carcinoma undergoing definitive radiotherapy (RT) or chemo-RT (CRT) in a single institution. One hundred and thirty-two patients with newly diagnosed locally advanced laryngeal carcinoma were included in this study retrospectively. All patients were treated with definitive RT or CRT. The tumor and metastatic lymph nodes received 70 Gy. Subclinical disease (low-risk and high-risk area) was irradiated 50-60 Gy prophylactically. Unintentional WL ≥5% was defined as the "critical level." Bodyweight was evaluated on the 1st day of RT and once a week during RT. Caloric needs were calculated as 25-30 kcal/kg/day. Median follow-up was 17.8 months (range: 2.35-85 months). During treatment, there was a statistically significant WL in patients (P = 0.004). WL was ≥5% in 62 (47%) of the patients. There was a statistically significant relationship between WL and tumor differentiation (P = 0.004), completion of treatment (P = 0.004), WHO performance status (P < 0.0001), T stage (P = 0.003), N stage (P = 0.049), and supraglottic tumor location (P = 0.005). In the univariate analysis, WL, WHO performance status, T stage, N stage, tumor localization, and tumor differentiation, were seen to affect OS. Additionally, WL, WHO performance status, N stage, and tumor differentiation were prognostic factors for PFS. In the multivariate analysis, it was observed that only WL and WHO performance status were significant factors for both OS (P = 0.001, and P < 0.01) and PFS (P < 0.001, and P < 0.001), respectively. Three-year OS and PFS was 50.3% and 19.5% for patients with WL versus 77.8% and 49.0% for patients without WL. It is clear that WL has prognostic significance in patients who have undergone definitive RT or CRT due to locally advanced laryngeal carcinoma. In particular, it should be taken into consideration that patients with supraglottic tumor, lymph node involvement, and poor performance status are at greater risk for WL.

High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy

PurposeTumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer.Materials and methodsTMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel.ResultsThe study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy.ConclusionThese data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy.Secondary abstractThis retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.

The Relationship Between Androgen Deprivation Therapy Duration and External Beam Radiotherapy With or Without a Brachytherapy Boost in High-Risk Prostate Cancer

The use/prolongation of androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT) improves distant metastasis outcomes in patients with high-risk prostate cancer. The optimal duration of ADT when adding a brachytherapy boost (EBRT+BT) remains unknown.A total of 2935 patients who received treatment across 15 institutions between 2000-2014 were identified (1827 treated with EBRT and 1108 with EBRT+BT). Three broad ADT strata were defined: no ADT, 1-18 months ADT, and 18-36 months ADT. Fine-Gray competing risk regression models evaluating the association between differing ADT duration strata and time to distant metastasis (DM) were developed. Models were adjusted for ln (initial PSA), clinical T stage, Gleason grade group, age at treatment, treatment type, and interaction between ADT duration and treatment. A continuous, non-linear relationship between ADT duration and DM was investigated in the overall cohort and within the EBRT and EBRT+BT cohorts using a restricted cubic spline transformation with 4 knots. Splines were adjusted for the same covariates.Median follow-up was 8 years (IQR, 5-11.3 years). ADT duration was significantly greater in patients treated with EBRT (median 18 months vs. 8 months, P < 0.001). A substantial proportion of patients did not receive any ADT (26.2% and 14.9% of those undergoing EBRT and EBRT+BT, respectively). Overall, DM rates were improved with adding 1-18 months of ADT or 18-36 months of ADT versus no ADT (sHR 0.66 and 0.43, respectively). DM rates were also lower after 18-36 months vs. 1-18 months (sHR 0.64). No significant interaction between treatment type and ADT duration was seen. Based on spline analysis, the optimal durations of ADT were 26 months for the total cohort and patients receiving EBRT and 22.5 months for patients receiving EBRT+BT. However, the incremental benefit of prolonged time to DM per month ADT added appears to be more pronounced in patients receiving EBRT than in those undergoing combined EBRT+BT treatment.A clear relationship between ADT duration and DM risk following definitive radiotherapy in patients with HRPCa was seen, with durations of 18-36 months being associated with the lowest risk of DM. The lack of a significant interaction between ADT duration and treatment type implies this relationship persists even in patients receiving EBRT+BT. However, the magnitude of this benefit may differ, and prospective evidence seems warranted to determine the optimal duration of ADT in patients receiving of EBRT+BT.