Modulation of CD8+ T Cell Responses by Radiotherapy-Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest in the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials to evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are currently undergoing. In this review, we summarize the current status of knowledge regarding the changes in CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biological mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

Evaluation of the dosimetric and radiobiological parameters in four radiotherapy regimens for synchronous bilateral breast cancer.

This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters. Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions-IMRT using a single isocenter (IMRT_Iso1), VMAT using a single isocenter (VMAT_Iso1), IMRT using dual isocenters (IMRT_Iso2), and VMAT using dual isocenters (VMAT_Iso2). A dose of 42.56 Gy in 16 fractions was prescribed for the planning target volume (PTV). All plans were calculated using the Acuros XB algorithm and a photon optimizer for a 6-MV beam of a Vital Beam linear accelerator. PTV-related dosimetric parameters were analyzed. Further, the homogeneity index, conformity index, and conformation number were computed to evaluate plan quality. Dosimetric parameters were also measured for the organs at risk (OARs). In addition, the equivalent uniform dose corresponding to an equivalent dose related to a reference of 2 Gy per fraction, the tumor control probability, and the normal tissue complication probability were calculated based on the dose-volume histogram to investigate the radiobiological impact on PTV and OARs. IMRT_Iso1 exhibited similar target coverage and a certain degree of dosimetric improvement in OAR sparing compared to the other techniques. It also exhibited some radiobiological improvement, albeit insignificant. Although IMRT_Iso1 significantly increased monitor unit compared to VMAT_Iso1, which is the best option in terms of delivery efficiency, there was only a 22% increase in delivery time. Therefore, in conclusion, IMRT_Iso1, the complete treatment of which can be completed using a single setup, is the most effective method for treating SBBC.

Mass Fabrication of 3D Silicon Nano-/Microstructures by Fab-Free Process Using Tip-Based Lithography.

Methods for the mass fabrication of 3D silicon (Si) microstructures with a 100 nm resolution are developed using scanning probe lithography (SPL) combined with metal-assisted chemical etching (MACE). Protruding Si structures, including Si nanowires of over 10 µm in length and atypical shaped Si nano- and micropillars, are obtained via the MACE of a patterned gold film (negative tone) on Si substrates by dip-pen nanolithography (DPN) with polymer or by nanoshaving alkanethiol self-assembled monolayers (SAMs). Furthermore, recessed Si structures with arbitrary patterning and channels less than 160 nm wide and hundreds of nanometers in depth are obtained via the MACE of a patterned gold film (positive tone) on Si substrates by alkanethiol DPN. As an example of applications using protruded Si structures, nanoimprinting in an area of up to a centimeter is demonstrated through 1D and 2D SPL combined with MACE. Similarly, submicrometer polydimethylsiloxane (PDMS) stamps are employed over millimeter-scale areas for applications using recessed Si structures. In particular, the mass production of arbitrarily shaped Si microparticles at submicrometer resolution is developed using silicon-on-insulator substrates, as demonstrated using optical microresonators, surface-enhanced Raman scattering templates, and smart microparticles for fluorescence signal coding.

Risk Stratification Using Neoadjuvant Rectal Score in the Era of Neoadjuvant Chemoradiotherapy: Validation With Long-term Outcome Data.

BACKGROUND: Despite the widespread use of neoadjuvant chemoradiotherapy, there is no prognostic surrogate marker established in locally advanced rectal cancer. OBJECTIVE: This study evaluated the role of neoadjuvant rectal score as a prognostic factor to stratify individual-level risks of survival and tumor recurrence. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at the Seoul National University Hospital. PATIENTS: A total of 397 patients who underwent chemoradiotherapy plus total mesorectal excision were analyzed. INTERVENTIONS: There was no intervention. MAIN OUTCOME MEASURES: Harrell C statistic and receiver operating characteristic analysis, as well as Cox regression analysis, were used to assess the prognostic strength. RESULTS: The low (<8), intermediate (8-16), and high (>16) neoadjuvant rectal score groups included 91 (23%), 208 (52%), and 98 patients (25%). A high neoadjuvant rectal score was independently associated with inferior overall survival and disease-free survival (p = 0.011 and 0.008). Regarding the prognostic models adjusted for neoadjuvant rectal score (I) and ypT/N stage (II), the c-index was higher in model I (0.799 and 0.787, p = 0.009 for overall survival; 0.752 and 0.743, p = 0.093 for disease-free survival). The predictive ability of the neoadjuvant rectal score was superior to tumor regression grade, ypT, and ypN in the receiver operating characteristic analyses (p < 0.05 for all). Adjuvant chemotherapy was associated with better overall and disease-free survival (p = 0.003 and 0.052) in the high neoadjuvant rectal score group. LIMITATIONS: Potential selection bias attributed to the retrospective study design was a limitation. CONCLUSIONS: We verified the applicability of the neoadjuvant rectal score to stratify the relapse risk at the individual level for patients with stage II/III rectal cancer undergoing neoadjuvant chemoradiotherapy. Additional studies are needed to validate the usability of neoadjuvant rectal score levels as a determinant of adjuvant strategy. See Video Abstract at http://links.lww.com/DCR/B354. ESTRATIFICACIÓN DE RIESGO UTILIZANDO LA PUNTUACIÓN RECTAL NEOADYUVANTE EN LA ERA DE LA QUIMIORRADIOTERAPIA NEOADYUVANTE: VALIDACIÓN CON DATOS DE RESULTADOS A LARGO PLAZO: A pesar del uso generalizado de la quimiorradioterapia neoadyuvante, no existe un marcador subrogado pronóstico establecido en el cáncer de recto localmente avanzado.Este estudio evaluó el papel de la puntuación rectal neoadyuvante como factor pronóstico para estratificar los riesgos a nivel individual de supervivencia y recurrencia tumoral.Este es un estudio retrospectivo.Este estudio se realizó en el Hospital de la Universidad Nacional de Seúl.Se analizaron un total de 397 pacientes que se sometieron a quimiorradioterapia más escisión mesorrectal total.No hubo intervención.El análisis estadístico C de Harrell y las características operativas del receptor, así como el análisis de regresión de Cox, se utilizaron para evaluar la fuerza pronóstica.Los grupos de puntaje rectal neoadyuvante bajo (<8), intermedio (8-16) y alto (> 16) incluyeron 91 (23%), 208 (52%) y 98 (25%) pacientes, respectivamente. Una puntuación rectal neoadyuvante alta se asoció independientemente con una supervivencia general y una supervivencia libre de enfermedad inferiores (p = 0.011 y 0.008, respectivamente). Con respecto a los modelos pronósticos ajustados por la puntuación rectal neoadyuvante (I) y el estadio ypT/N (II), el índice c fue mayor en el modelo I (0.799 y 0.787, p = 0.009 para la supervivencia general; 0.752 y 0.743, p = 0.093 para supervivencia libre de enfermedad). La capacidad predictiva de la puntuación rectal neoadyuvante fue superior al grado de regresión tumoral, ypT y ypN en los análisis de características operativas del receptor (p <0.05 para todos). La quimioterapia adyuvante se asoció con una mejor supervivencia global y libre de enfermedad (p = 0.003 y 0.052, respectivamente) en el grupo de puntaje rectal neoadyuvante alto.El sesgo de selección potencial debido al diseño retrospectivo del estudio fue la limitación.Verificamos la aplicabilidad de la puntuación rectal neoadyuvante para estratificar el riesgo de recurrencia a nivel individual para pacientes con cáncer rectal en estadio II/III sometidos a quimiorradioterapia neoadyuvante. Se necesitan más estudios para validar la usabilidad de los niveles de puntuación rectal neoadyuvante como determinante de la estrategia adyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B354.

Optimal planning strategy among various arc arrangements for prostate stereotactic body radiotherapy with volumetric modulated arc therapy technique.

BACKGROUND: The aim of this study was to determine the optimal strategy among various arc arrangements in prostate plans of stereotactic body radiotherapy with volumetric modulated arc therapy (SBRT-VMAT). PATIENTS AND METHODS: To investigate how arc arrangements affect dosimetric and biological metrics, SBRT-VMAT plans for eighteen patients were generated with arrangements of single-full arc (1FA), single-partial arc (1PA), double-full arc (2FA), and double-partial arc (2PA). All plans were calculated by the Acuros XB calculation algorithm. Dosimetric and radiobiological metrics for target volumes and organs at risk (OARs) were evaluated from dosevolume histograms. RESULTS: All plans were highly conformal (CI<1.05, CN=0.91) and homogeneous (HI=0.09-0.12) for target volumes. For OARs, there was no difference in the bladder dose, while there was a significant difference in the rectum and both femoral head doses. Plans using 1PA and 2PA showed a strong reduction to the mean rectum dose compared to plans using 1FA and 2FA. Contrastively, the D2% and mean dose in both femoral heads were always lower in plans using 1FA and 2FA. The average tumor control probability and normal tissue complication probability were comparable in plans using all arc arrangements. CONCLUSIONS: The use of 1PA had a more effective delivery time and produced equivalent target coverage with better rectal sparing, although all plans using four arc arrangements showed generally similar for dosimetric and biological metrics. However, the D2% and mean dose in femoral heads increased slightly and remained within the tolerance. Therefore, this study suggests that the use of 1PA is an attractive choice for delivering prostate SBRT-VMAT.

Preoperative chemoradiotherapy for elderly patients with locally advanced rectal cancer-a real-world outcome study.

OBJECTIVE: Preoperative chemoradiotherapy has been established as a standard treatment for locally advanced rectal cancer. It is unclear whether preoperative chemoradiotherapy is truly beneficial in the elderly patients. Our aim was to assess the impact of age on the treatment tolerance and clinical outcomes. METHODS: We retrospectively analyzed 160 consecutive patients with clinical stage T3-4, and/or lymph node positive tumors who received preoperative chemoradiotherapy from May 2003 to December 2010 at a single hospital. Treatment tolerance and outcomes were compared between patients ≥70 years (N = 56) and <70 years (N = 104). RESULTS: There was no disparity in the achievement of prescribed radiation dose and dose reduction of chemotherapy between two groups. Pathologic complete response rate (15.6% vs. 16.0%) and sphincter preservation rate (91.1% vs. 95.0%; P = 0.459) were not significantly different. The 3-year disease-free survival of older vs. younger patients was 77.8% vs. 92.3% and 5-year disease-free survival was 60.0% vs. 78.6%, respectively (P = 0.023). In multivariable analysis, age was significantly associated with disease-free survival (P = 0.033) but comorbidities were not (P = 0.092). However, both age (hazard ratio, 2.331; P = 0.028) and comorbidities (hazard ratio, 2.772; P = 0.031) were significantly associated with overall survival as well as clinical stage. Anemia was the only adverse effect more prominent in older patients. CONCLUSIONS: Older patients showed non-inferior compliance and equivalent pathologic complete response rates without an increased incidence of treatment complications with preoperative chemoradiotherapy. More comprehensive consideration than age alone is warranted in the decision of applying preoperative chemoradiotherapy to elderly patients with rectal cancer.

Comparison of Dosimetric Performance among Commercial Quality Assurance Systems for Verifying Pretreatment Plans of Stereotactic Body Radiotherapy Using Flattening-Filter-Free Beams.

The purpose of this study was to compare the performance of different commercial quality assurance (QA) systems for the pretreatment verification plan of stereotactic body radiotherapy (SBRT) with volumetric arc therapy (VMAT) technique using a flattening-filter-free beam. The verification for 20 pretreatment cancer patients (seven lung, six spine, and seven prostate cancers) were tested using three QA systems (EBT3 film, I'mRT MatriXX array, and MapCHECK). All the SBRT-VMAT plans were optimized in the Eclipse (version 11.0.34) treatment planning system (TPS) using the Acuros XB dose calculation algorithm and were delivered to the Varian TrueBeam® accelerator equipped with a high-definition multileaf collimator. Gamma agreement evaluation was analyzed with the criteria of 2% dose difference and 2 mm distance to agreement (2%/2 mm) or 3%/3 mm. The highest passing rate (99.1% for 3%/3 mm) was observed on the MapCHECK system while the lowest passing rate was obtained on the film. The pretreatment verification results depend on the QA systems, treatment sites, and delivery beam energies. However, the delivery QA results for all QA systems based on the TPS calculation showed a good agreement of more than 90% for both the criteria. It is concluded that the three 2D QA systems have sufficient potential for pretreatment verification of the SBRT-VMAT plan.

Elective pelvic versus prostate bed-only salvage radiotherapy following radical prostatectomy: A propensity score-matched analysis.

PURPOSE: To compare the impact of elective whole pelvic radiotherapy (WPRT) versus prostate bed-only radiotherapy (PBRT) on biochemical relapse-free survival (bRFS) in prostate cancer patients treated with salvage radiotherapy following radical prostatectomy (RP). PATIENTS AND METHODS: In our database, 163 lymph node-negative prostate cancer patients who had undergone salvage radiotherapy (SRT) for biochemical relapse after RP between September 2004 and April 2012 were identified. PBRT was administered to 134 patients (the PBRT group), while the remaining 29 patients (the WPRT group) received WPRT. RESULTS: Median follow-up was 57 months (range 18-122 months). In the propensity score-matched cohort, the 4-year bRFS of the WPRT group was significantly higher compared to the PBRT group (63.1 vs. 43.4%, p = 0.034). Subgroup analysis showed that the bRFS of patients who had two or more risk factors (seminal vesicle invasion, Roach score for lymph node invasion ≥ 45%, and number of harvested lymph nodes ≤ 5) and were treated with WPRT was significantly improved compared to those who received PBRT (hazard ratio, HR 0.33; 95% confidence interval, CI 0.13-0.83; p = 0.018). CONCLUSION: Elective WPRT for SRT may improve bRFS in patients with unfavorable risk factors. These results need to be confirmed by a prospective randomized trial.

No survival benefit with early incorporation of thoracic radiotherapy using daily fractionation in patients with limited-stage small cell lung cancer undergoing chemoradiotherapy in the modern era: A systematic review and meta-analysis.

BACKGROUND: When concurrent chemoradiotherapy (CCRT) is administered for limited-stage small cell lung cancer (LS-SCLC), the early incorporation of thoracic radiotherapy (TRT) is generally recommended. However, it is controversial if this approach is really beneficial with most commonly used daily fractionated TRT in the modern era. METHODS: A systematic literature search was performed using several databases following the PRISMA guidelines from Jan 2000 to Nov 2022. We excluded twice-daily TRT-based studies. The hazard ratio (HR) for survival following late TRT as a primary effect size was pooled from comparisons within individual studies according to the timing of daily fractionated TRT (early vs. late). RESULTS: A total of 10 studies including 10,164 analyzable patients met all inclusion criteria. 'Early' timing usually referred to TRT within 1-2 cycles of concurrent chemotherapy. The pooled results demonstrated that the risk of death was not significantly increased following late TRT compared with early TRT (HR 1.01, 95% CI 0.84-1.20, p = 0.94). All sensitivity analysis and planned subgroup analyses showed similar results. In comparison with early TRT, late TRT did not significantly increase the risk of progression (HR 0.94, 95% CI 0.80-1.11, p = 0.48). Furthermore, late TRT was beneficial in alleviating grade 3 or higher esophagitis (OR 0.42, p = 0.01), but no significant differences was found in pneumonitis (OR 0.62, p = 0.38), and neutropenia (OR 0.57, p = 0.11). No evidence of publication bias was found. CONCLUSIONS: This is the first meta-analysis to support the late incorporation of TRT in managing patients with LS-SCLC undergoing daily fractionated CCRT in the modern era. This approach may not compromise survival and can prevent severe acute toxicities. Further prospective studies of the daily fractionated TRT timing are warranted.

Regional lymph node recurrence after stereotactic body radiation therapy for lung cancer: Patterns of recurrence, treatment approaches, and clinical outcomes (KROG 21-09).

PURPOSE: To present the multi-institutional data on patterns of recurrence, treatment approaches, and clinical outcomes for regional lymph node (LN) recurrence after stereotactic body radiation therapy (SBRT) for primary lung cancer. MATERIALS AND METHODS: The medical records of 114 patients who experienced regional LN recurrence as the first recurrence after lung SBRT were retrospectively reviewed. Patterns of recurrence were classified as local recurrence, regional recurrence, and distant metastasis. Clinical outcomes including progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Half of the patients had regional LN recurrence only. The most common simultaneous recurrence was distant metastasis (38.6 %). Common sites of regional recurrence were ipsilateral hilar (47.2 %), ipsilateral upper mediastinal (40.6 %), and subcarinal (42.5 %) LN stations. 24 (21.1 %) patients underwent salvage radiation therapy (RT), and 44 (38.6 %) patients underwent palliative treatment. Better OS was observed in the salvage RT group (p = 0.025). The 1-year PFS and OS rates were 27.7 % and 55.2 %, respectively, with salvage RT, 14.0 % and 39.9 %, respectively, with palliative treatment, and 22.8 % and 26.8 %, respectively, with no additional treatment. Multivariate analysis showed that salvage RT (PFS, HR 0.463, p = 0.050; OS, HR 0.312, p = 0.002), palliative treatment (PFS, HR 0.436, p = 0.013; OS, HR 0.553, p = 0.050), and simultaneous distant metastasis (PFS, HR 2.335, p = 0.005; OS, HR 1.726, p = 0.054) affected clinical outcomes. CONCLUSION: Many cases of regional LN recurrence are confined to the locoregional area of patients, and appropriate treatment can improve the prognosis of these patients.

GLUT-1 may predict metastases and death in patients with locally advanced rectal cancer.

Introduction: Glucose transporter-1 (GLUT-1) has been studied as a possible predictor for survival outcomes in locally advanced rectal cancer (LARC). Methods: We aimed to investigate the prognostic role of GLUT-1 in LARC using the data of 208 patients with clinical T3-4 stage and/or node-positive rectal adenocarcinoma, all of whom underwent neoadjuvant chemoradiotherapy (CRT) and subsequent total mesorectal excision (TME). Both pre-CRT and post-CRT specimens were immunohistologically stained for GLUT-1. Patients were classified into GLUT-1-positive and GLUT-1-negative groups and distant metastasis-free survival (DMFS) and overall survival (OS) was analyzed and compared. Results: At a median follow-up of 74 months, post-CRT GLUT-1 status showed a significant correlation with worse DMFS (p=0.027, HR 2.26) and OS (p=0.030, HR 2.30). When patients were classified into 4 groups according to yp stage II/III status and post-CRT GLUT-1 positivity [yp stage II & GLUT-1 (-), yp stage II & GLUT-1 (+), yp stage III & GLUT-1 (-), yp stage III & GLUT-1 (+)], the 5-year DMFS rates were 92.3%, 63.9%, 65.4%, and 46.5%, respectively (p=0.013). GLUT-1 (-) groups showed markedly better outcomes for both yp stage II and III patients compared to GLUT-1 (+) groups. A similar tendency was observed for OS. Discussion: In conclusion, post-CRT GLUT-1 may serve as a prognostic marker in LARC.

Role of prognostic nutritional index in postoperative radiotherapy for non-small cell lung cancer.

BACKGROUND: The prognostic nutritional index (PNI) is known to be correlated with clinical outcomes in non-small cell lung cancer (NSCLC) patients. However, its role has not been studied in patients who have undergone postoperative radiotherapy (PORT). This study aimed to investigate the relationship between PNI and survival and recurrence in NSCLC patients with PORT. METHODS: We reviewed 97 stage I-III NSCLC patients who received PORT between January 2006 and December 2016 at our institution. We obtained PNI values for both pre-RT (within 1 month before PORT) and post-RT (within 2 months after PORT) by using serum albumin and lymphocyte count. A cutoff value for PNI was determined by the receiver operating characteristic curve (ROC). The median follow-up period was 52.8 months. RESULTS: The ROC curve of post-RT PNI exhibited a higher area under the curve (AUC 0.68, cut-off: 47.1) than that of pre-RT PNI (AUC 0.55, cutoff: 50.3), so the group was divided into high post-RT PNI (> 47.1) and low post-RT PNI ( ≤ 47.1). The five-year overall survival rate (OS) was 66.2% in the high post-RT group, compared with 41.8% in the low post-RT PNI group (p = 0.018). Those with both low pre-RT and low post-RT PNI had the worst five-year OS of 31.1%. Post-RT PNI (HR 0.92, p = 0.003) was an independent risk factor for mortality. CONCLUSIONS: PNI after PORT was significantly associated with survival. This finding suggests that PNI can be used as a prognostic marker.

Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015.

PURPOSE: This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015. MATERIALS AND METHODS: The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020. RESULTS: We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non-small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%). CONCLUSION: In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

20 year experience of postoperative radiotherapy in IB-IIA cervical cancer patients with intermediate risk factors: impact of treatment period and concurrent chemotherapy.

OBJECTIVE: To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors. METHODS: Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n=56) or CCRT (n=54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n=39), RT 2000-2010 (n=17) and CCRT 2000-2010 (n=54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n=48). RESULTS: Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p=0.012) and distant metastasis (p=0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p<0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups. CONCLUSIONS: This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.

Survival impact of prophylactic cranial irradiation in small-cell lung cancer in the modern era of magnetic resonance imaging staging.

BACKGROUND: In the modern era of magnetic resonance imaging (MRI) staging, the benefit of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC) has been controversial. This study evaluated the prognostic impact of PCI in patients with limited- or extensive-stage SCLC who had no brain metastases at diagnosis according to MRI. METHODS: Data from newly diagnosed patients in 2014 from the Korean Association for Lung Cancer Registry database were used. Patients with limited- or extensive-stage SCLC who had no brain metastases according to MRI were identified. Univariate and multivariate survival analyses were conducted to assess the prognostic association of PCI. RESULTS: Of 107 and 122 patients with limited- and extensive-stage SCLC, 24% and 14% received PCI, respectively. In the limited-stage SCLC group, the 2-year overall survival (OS) rates of patients who received PCI and those who did not were 50% and 29% (P = 0.018), respectively. However, there was no significant difference in OS for patients with extensive-stage SCLC (P = 0.336). After adjusting for other covariates, PCI was found to be associated with improved OS in the limited-stage SCLC group (P = 0.005). Based on the time-course hazard rate function plots in the limited-stage SCLC group, the OS benefit of PCI was maximized within the first year of follow-up. CONCLUSIONS: In the modern era of MRI staging, PCI might be beneficial for patients with limited-stage SCLC but not for those with extensive-stage SCLC. Further studies with a large sample size are needed to verify the prognostic association of PCI.

Prediction and clinical impact of delayed lymphopenia after chemoradiotherapy in locally advanced non-small cell lung cancer.

Introduction: The dosimetric factors of radiotherapy have an acute impact on the host immune system during chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, even after CRT, a substantial number of patients remain immunosuppressed with delayed lymphopenia. Therefore, we aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia after CRT in locally advanced NSCLC. Materials and methods: We retrospectively reviewed 272 patients with locally advanced NSCLC who received definitive CRT from January 2012 to August 2020. Differential blood count data, including serum albumin values, were obtained at baseline, during and at first follow up after CRT. Acute and delayed lymphopenia events were defined as grade III/IV lymphopenia developed during or 4-12 weeks after CRT completion, which accounted for 84% and 10% of cases, respectively. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated. Results: Multivariate analysis revealed that patients with delayed lymphopenia were associated with inferior overall survival (HR 2.53, P = 0.001) and progression-free survival (HR 1.98, P = 0.006). However, there was no significant survival difference between groups stratified by acute lymphopenia. On multivariable logistic regression models, lung V5, baseline ALC, during-CRT ALC, and albumin nadir were significant predictors for delayed lymphopenia. Furthermore, the nomogram for delayed lymphopenia based on these variables had good discrimination (area under the curve, 0.905). Conclusions: In this study, we investigated the prognostic significance of delayed lymphopenia and identified clinico-dosimetric parameters to predict delayed lymphopenia.

Induction FOLFIRINOX followed by stereotactic body radiation therapy in locally advanced pancreatic cancer.

Introduction: FOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC. Methods: To this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival. Results: Fifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3-28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4-30.3) and 16.7 months (95% CI: 13.0-20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042-3.930, p = 0.037). Conclusion: Our findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.

Efficacy of geriatric multidisciplinary oncology clinic in the surgical treatment decision-making process for frail elderly patients with colorectal cancer.

Purpose: Multidisciplinary care has become a cornerstone of colorectal cancer management. To evaluate the clinical efficacy of a geriatric multidisciplinary oncology clinic (GMOC), we analyzed the surgical treatment decision-making process and outcomes. Methods: This retrospective single-center study reviewed the data of patients aged ≥65 years who participated in the GMOC at a tertiary referral hospital between 2015 and 2021. The clinical adherence rate, comprehensive geriatric assessment, and a multidimensional frailty score (MFS) were obtained. The groups that were recommended and not recommended for surgery were compared, analyzing the factors impacting the decision and 1-year survival outcomes. Furthermore, the postoperative complications of patients who underwent surgery were evaluated. Results: A total of 165 patients visited the GMOC, and 74 had colorectal cancer (mean age, 85.5 years [range, 81.2-89.0 years]). Among patients with systemic disease (n = 31), 7 were recommended for surgery, and 5 underwent surgery. Among patients with locoregional disease (n = 43), 18 were recommended for surgery, and 12 underwent surgery. Patients recommended and not recommended for surgery had significantly different activities of daily living (ADL) (P = 0.024), instrumental ADL (P = 0.001), Mini-Mental State Examination (P = 0.014), delirium risk (P = 0.039), and MFS (P = 0.001). There was no difference in the 1-year overall survival between the 2 groups (P = 0.980). Of the 17 patients who underwent surgery, the median (interquartile range) of operation time was 165.0 minutes (120.0-270.0 minutes); hospital stay, 7.0 days (6.0-8.0 days); and 3 patients had wound complications. Conclusion: Proper counseling of patients through the GMOC could lead to appropriate management and favorable outcomes.

Radiogenomic and Deep Learning Network Approaches to Predict KRAS Mutation from Radiotherapy Plan CT.

BACKGROUND/AIM: We aimed to investigate the role of radiogenomic and deep learning approaches in predicting the KRAS mutation status of a tumor using radiotherapy planning computed tomography (CT) images in patients with locally advanced rectal cancer. PATIENTS AND METHODS: After surgical resection, 30 (27.3%) of 110 patients were found to carry a KRAS mutation. For the radiogenomic model, a total of 378 texture features were extracted from the boost clinical target volume (CTV) in the radiotherapy planning CT images. For the deep learning model, we constructed a simple deep learning network that received a three-dimensional input from the CTV. RESULTS: The predictive ability of the radiogenomic score model revealed an AUC of 0.73 for KRAS mutation, whereas the deep learning model demonstrated worse performance, with an AUC of 0.63. CONCLUSION: The radiogenomic score model was a more feasible approach to predict KRAS status than the deep learning model.

Retropharyngeal lymph node-sparing radiotherapy in patients with oropharyngeal carcinoma.

PURPOSE: In radiotherapy for head and neck cancer, it is crucial to define the appropriate treatment volume to determine treatment outcome and toxicity. We examined the feasibility of omitting elective high retropharyngeal lymph node (RPLN) irradiation in patients with oropharyngeal cancer. MATERIALS AND METHODS: We performed a retrospective review of 189 patients with oropharyngeal squamous cell carcinoma who were treated with definitive or postoperative radiation therapy between 2009 and 2016. Of them, 144 (76.2%) underwent ipsilateral RPLN irradiation up to the superior border of the C1 vertebral body, while the other 45 (23.8%) were irradiated up to the transverse process of the C1 vertebra. High RPLN-treated and spared group were propensity matched based on key clinical variables. RESULTS: During the follow-up period, only three patients (one in the high RPLN-treated group and two in the high RPLN-spared group) developed RPLN recurrence. There were no significant between-group differences in 5-year locoregional failure-free survival (82.8% vs. 90.6%; p = 0.14), distant metastasis-free survival (93.1% vs. 93.3%; p = 0.98) and RPLN failure-free survival (99.3% vs. 95.0%; p = 0.09). In the matched groups, high RPLN-spared patients received a lower mean ipsilateral parotid gland dose (mean, 20.8 Gy vs. 29.9 Gy; p < 0.001) and had a lower incidence of chronic xerostomia (grade 0, 43.5% vs. 13.0%; p = 0.023) at 1 year after radiotherapy compared with high RPLN-treated patients. CONCLUSION: Omission of ipsilateral high RPLN irradiation seems safe, and reduces the incidence of chronic xerostomia in patients with oropharyngeal squamous cell carcinoma.