Median Locoregional Progression-free Survival Research Articles

Clinical efficacy analysis of radioactive 125I particle implantation for the treatment of pelvic local recurrence of cervical cancer after radiotherapy.

To explore the efficacy of CT-guided iodine-125 (125I) radioactive particle implantation for the treatment of pelvic local recurrence of cervical cancer after radiotherapy. To analyze clinical data of 46 patients with pelvic local recurrence of cervical cancer after radiotherapy, who underwent 125I particle implantation, post-operative follow-up using Kaplan-Meier method to calculate the rate of local control, and observation of complications. Univariate and multi-factorial analyses were performed with log-rank test and Cox regression statistical method to observe changes in serum SCC-Ag and CEA levels. A total of 57 lesions in 46 patients had a short-term local control rate of 87.72% (50/57) and effective rate of 68.42% (39/57). As of the end of follow-up, the median local progression-free survival time of 46 patients was 12.2 (range, 3.5-32) months, the median overall survival time was 16.3 (range, 3.5-40) months, with 1-year and 2-year OS of 63.04% and 41.30%. Univariate and multi-factorial analyses suggested that local recurrent mass size and recurrence site were the main factors affecting survival. Loco-regional progression-free survival (LPFS) time was 15.5 and 11.25 months in cases with recurrent mass diameter < 3 cm and ≥ 3 cm, respectively (χ2 = 10.83, p = 0.001 < 0.05). In patients with pelvic wall recurrence and central recurrence, the time to LPFS was 15.80 and 10.00 months, respectively (χ2 = 8.833, p = 0.0030 < 0.05). Tumor markers serum SCC-Ag and CEA decreased to different degrees after treatment, and the difference was statistically significant. The median LPFS in the SCC-Ag ≤ 3.5 ng/ml group was significantly higher than that in the SCC-Ag > 3.5 ng/ml group (χ2 = 4.241, p = 0.036 < 0.05). No serious post-operative complications were observed. CT-guided 125I seed implantation has significant short-term efficacy in the treatment of pelvic local recurrence of cervical cancer after radiotherapy. It can improve the effective rate in patients with initial clinical stage II, especially in those with locally recurrent masses < 3 cm and in those with a recurrence in the pelvic wall.

Could 18-FDG PET-CT Radiomic Features Predict the Locoregional Progression-Free Survival in Inoperable or Unresectable Oesophageal Cancer?

Simple SummaryAlmost 20% of patients with a locally advanced oesophageal cancer presented long-term local control after exclusive chemoradiotherapy (CRT) and could potentially avoid surgery and its morbidity and mortality. With the aim of identifying the patients that would present long-term locoregional control, we analysed in this study the potential of some pre-treatment positron-emission tomography-computed tomography (PET-CT)-based features in predicting long-term responses and local control in patients treated with definitive CRT. Our results show that radiomics allows for the identification of patients with long-term locoregional control. If confirmed on larger populations, our results could allow the identification of patients who are good responders to CRT, and who could potentially avoid surgery.Background: We evaluated the value of pre-treatment positron-emission tomography–computed tomography (PET-CT)-based radiomic features in predicting the locoregional progression-free survival (LR-PFS) of patients with inoperable or unresectable oesophageal cancer. Material and Methods: Forty-six patients were included and 230 radiomic parameters were extracted. After a principal component analysis (PCA), we identified the more robust radiomic parameters, and we used them to develop a heatmap. Finally, we correlated these radiomic features with LR-PFS. Results: The median follow-up time was 17 months. The two-year LR-PFS and PFS rates were 35.9% (95% CI: 18.9–53.3) and 21.6% (95%CI: 10.0–36.2), respectively. After the correlation analysis, we identified 55 radiomic parameters that were included in the heatmap. According to the results of the hierarchical clustering, we identified two groups of patients presenting statistically different median LR-PFSs (22.8 months vs. 9.9 months; HR = 2.64; 95% CI 0.97–7.15; p = 0.0573). We also identified two radiomic features (“F_rlm_rl_entr_per” and “F_rlm_2_5D_rl_entr”) significantly associated with LR-PFS. Patients expressing a “F_rlm_2_5D_rl_entr” of <3.3 had a better median LR- PFS (29.4 months vs. 8.2 months; p = 0.0343). Patients presenting a “F_rlm_rl_entr_per” of <4.7 had a better median LR-PFS (50.4 months vs. 9.9 months; p = 0.0132). Conclusion: We identified two radiomic signatures associated with a lower risk of locoregional relapse after CRT.

Locoregional progression-free survival of bone metastases from differentiated thyroid cancer.

To evaluate the locoregional progression-free survival (LPFS) of bone metastatic lesions from differentiated thyroid cancer (DTC) after radioiodine therapy (RAIT) and to define its influencing factors, we performed a retrospective cohort analysis of 89 patients with bone metastases from DTC who received RAIT in our department over a 17-year period. The median follow-up time was calculated using the reverse Kaplan–Meier method. The log-rank test and a multivariate Cox proportional hazards regression model were performed in the analysis of prognostic indicators for LPFS. In this research, the median follow-up time for all patients was 47 (95% CI, 35.752–58.248) months, and that for patients with no progression was 42 months. The longest follow-up time was 109 months. The median LPFS time was 58 (95% CI, 32.602–83.398) months, and the 3- and 5-year LPFS probabilities were 57.8 and 45.1%, respectively. Multivariate analysis revealed bone structural changes as an independent risk factor for LPFS (P= 0.004; hazard ratio, 49.216; 95% CI, 3.558–680.704). Furthermore, the non–total-lesion uptake subgroup presented a worse LPFS than the total-lesion uptake subgroup in patients with structural bone lesions (P = 0.027). RAIT can improve the LPFS of radioiodine-avid bone metastases from DTC, especially those without bone structural changes.

Comparison and quantification of different concurrent chemotherapy regimens with radiotherapy in locally advanced non-small cell lung cancer: Clinical outcomes and theoretical results from an extended LQ and TCP model

PurposeTo develop a new radiobiological model and compare the efficacy of four concurrent chemotherapy regimens administered with radiotherapy in locally advanced non-small-cell lung cancer (LANSCLC) by in-field locoregional progression-free survival (LPFS). Materials and Methods151 LANSCLC patients were reviewed and divided into 5 groups according to their concurrent chemotherapy regimens, including 24 patients treated with radiotherapy alone, 30 treated with concurrent 4-week etoposide-cisplatin (EP), 26 with 3-week pemetrexed-cisplatin (AP), 37 with weekly paclitaxel-cisplatin (TP) and 34 with weekly docetaxel-cisplatin (DP). In-field LPFS and toxicities were compared among groups. A novel tumor control probability (TCP) model, LQRGC, incorporating four “R”s of radiobiology, Gompertzian tumor growth and chemotherapeutic effect, was related to in-field LPFS. Chemo-induced biologically effective doses (BEDs) in LQRGC/TCP model were used to quantify the concurrent chemotherapeutic efficacy. ResultsThe median follow-up time was 54.5 months. The weekly DP and 4-week EP groups had favorable median in-field LPFS (EP:46.2 months, AP:30.3 months, TP:12.2 months, DP: not reached, radiotherapy alone: 12.2 months, p = 0.001). The 4-week EP group had a higher incidence of ≥grade 3 leukopenia (EP:76.7%, AP:15.4%, TP:24.3%, DP:14.7%, radiotherapy alone: 12.5%, p < 0.001) than the other four. The LQRGC/TCP model fitted well with the in-field LPFS with the average absolute and relative fitting errors of 6.36% and 12.12%. The chemo-induced BEDs of EP, AP, TP and DP were 5.17, 0.63, 1.89 and 2.52 Gy, respectively. ConclusionThe LQRGC/TCP model achieved promising fitting accuracy for in-field LPFS. As quantified by the model, the 4-week EP and weekly DP showed higher chemo-induced BEDs when concurrently administered with radiotherapy in LANSCLC.

Exclusive Chemoradiotherapy With or Without Radiation Dose Escalation in Esophageal Cancer: Multicenter Phase 2/3 Randomized Trial CONCORDE (PRODIGE-26)

Increasing dose of chemoradiotherapy in locally advanced esophageal cancer unsuitable for surgery has been a matter of debate in the last 2 decades. Advances in tumor staging and radiation targeting with modern imaging and IMRT should allow further testing exclusive radiation dose escalation in esophageal cancer.We performed a multicenter, randomized, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 28 centers in France between 07/06/2011 and 11/10/2019. Eligible participants had confirmed stage I-III biopsy proven esophageal carcinoma, ECOG 0-2 and sufficient caloric intake. Patients were randomly assigned (1:1) to receive 50Gy in 25 fractions over 5 weeks (standard arm) or 66Gy in 33 fractions over 6.5 weeks (experimental arm). Elective nodal irradiation (40Gy) was delivered in both groups. Concomitant chemotherapy was FOLFOX-4 for 3 courses followed by 3 adjuvant courses. Random allocation to treatment groups was done by a central computerized randomization procedure by minimization, stratified by center, histology, weight loss, and technique of radiotherapy. The primary endpoint was 2-year locoregional progression-free survival (LRPFS).109 participants were randomly allocated to the 50Gy arm and 108 to the 66Gy group (intention-to-treat population). 177 men (81.6%) and 40 women (18.4%) were included with a mean age of 62.6 years (± 7.8). 191 patients (88.4%) had squamous cell cancer and 25 (11.6%) has adenocarcinoma. Most of the patients had stage III tumors (74% vs 26% for stage I-II). IMRT was delivered in 169 patients (80.1%) and 3D conformal in 42 patients (19.9%). 59 patients (54.1%) have died in the 50Gy group and 65 patients (60.2%) in the 66Gy group with a median follow up 35.3 months (range: 2.0-65.7) and 35.5 months (range: 1.3-60.7), respectively. Median overall survival was 25.2 months (95% CI 17.8-NR) in the 50Gy group and 23.5 months (14.5-32.2) in the 66Gy group (HR 1.14, 95% CI 0.82-1.59; P = 0.44). Median LRPFS was 16.2 months (95% CI 10.9-26.0) in the 50Gy group and 18.4 months (12.2-25.7) in the 66Gy group (HR 1.03, 95% CI 0.75-1.40; P = 0.88). The 2-year LRPFS rates were 42.7% (95% CI 33.2%-51.8%) and 43.8% (95% CI 34.1%-54.1%). No significant differences were recorded in the rates of late adverse events between the treatment groups (P = 0.14). The rates of grade 3/4 toxicities in the 50Gy group were 29.5%/0% and 24.0%/5.3% in the 66Gy group. 5 toxic deaths (4.6%) occurred in the 50Gy group and 7 (6.7%) in the 66Gy group. One and 2 toxic deaths out of the 5 in the 50Gy were related to radiotherapy or chemotherapy, respectively. Two and 3 out of the 7 toxic deaths in the 66Gy were related to radiotherapy or chemotherapy, respectively.Dose escalated chemoradiotherapy delivering 66Gy is not more toxic than 50Gy but did not improve locoregional progression-free survival. Chemoradiotherapy delivering 50Gy should be definitely admitted as a standard dose.

Efficacité et tolérance de la radiothérapie externe pour les patients atteints d'une récidive d'un carcinome différencié de la thyroïde

PurposeRadiation therapy is often the last resource treatment for cervical relapse in iodine refractory differentiated thyroid cancer. We present locoregional control data in patients with cervical relapse treated with curative intent radiation therapy with or without concomitant carboplatin. Material and methodsThis monocentric retrospective study gathered data on patients with differentiated thyroid carcinoma – vesicular or papillary – in relapse after thyroidectomy who received a curative intent cervical radiation therapy. Locoregional progression free survival (LRPFS), progression free survival (PFS), overall survival (OS) were gathered as well as acute and chronic adverse events assessed with the CTCAE v4. ResultsThirty-nine patients were consecutively included between 2005 and 2019. The median follow-up was 36.6months. Fifteen patients (38%) had a locoregional relapse, locoregional control at 2years was 66.7%. The median LRPFS was 48months [32.9–not reached] and the median overall survival 49months [38.8–not reached]. In multivariate analysis, initial incomplete resection was associated with poorer OS (HR: 24.39 [3.57–166.78], P=0.00113) and LRPFS (HR: 33.91 [4.46–257.61], P=0.00066), extra nodal spread was associated with poorer LRPFS (HR: 13.45 [1.81–99,76], P=0.011). ECOG performance status was associated with OS (HR: 5.11 [1.57–16.66], P=0.00688). Carboplatin association with radiation therapy was not associated with improved survivals (OS: P=0.34, LRPFS: P=0.84). The rate of acute grade 3 toxicities was 14%. ConclusionSalvage cervical radiation therapy was associated with a locoregional control of 66.7% at 2years with a reasonable toxicity rate. Carboplatin association with radiation therapy did not improve locoregional control nor overall survival in comparison with radiotherapy alone.

Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma.

Background:Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma.Materials and methods:Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC).Results:A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 versus 18.2 months, p = 0.02; PFS: 24.1 versus 7.1 months, p < 0.001). There was no survival difference between the BR and LAPC patients. The 1-year LC from SBRT was 74.1% and the median locoregional PFS was not reached for both BR and LAPC patients.Conclusions:iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials.

Hypofractionated intensity-modulated radiotherapy with concurrent chemotherapy for elderly patients with locally advanced pancreatic carcinoma

BackgroundIt is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC.MethodsWe retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed.ResultsFifteen patients received treatment during the study period. The median age was 78 years (range 75–86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0–1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3–36.8] and 13.5 (95% CI 6.4–20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50–93.1%) and 66.7% (95% CI 37.5–84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4–36.8) and 14.9 (95% CI 7.0–20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6–89.1%) and 66.7% (95% CI 37.5–84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4–5 non-haematologic acute or late toxicities were not observed.ConclusionsThe OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.

Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial

Background and purposeBoron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. Materials and methodsIn this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). ResultsEight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4–76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). ConclusionThese data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

Comparison between the effects of elective nodal irradiation and involved-field irradiation on long-term survival in thoracic esophageal squamous cell carcinoma patients: A prospective, multicenter, randomized, controlled study in China.

BackgroundThis study's initial results revealed significant decreases in treatment‐related esophagitis and pneumonitis cases in patients with thoracic esophageal squamous cell carcinoma (ESCC) treated with involved‐field irradiation (IFI), compared to elective nodal irradiation (ENI). This report outlines the long‐term trial results, specifically; overall survival (OS), progression‐free survival (PFS), metastasis‐free survival (MFS), and locoregional progression‐free survival (LRFS).Materials and MethodsStage II–III thoracic ESCC patients were assigned randomly, in a 1:1 ratio, into either the ENI or IFI arm. Radiation therapy was delivered once a day in 1.8‐2.0 Gy fractions to a total dose of 60.0‐66.0 Gy to the gross tumor volume and 50.0‐54.0 Gy to the clinical target volume. The primary endpoints were acute treatment‐related esophagitis and pneumonitis. The results for the primary endpoints were previously published in 2018. In this article, we analyzed the secondary endpoints including PFS, LRFS, MFS, and OS.ResultsBetween April 2012 and October 2016, 228 patients from nine participating centers in China were enrolled into this study and randomly assigned to two treatment groups. For ENI and IFI groups, respectively, the results showed similarity and were as follows: median PFS (20.3 months vs 21.4 months), OS (32.5 months vs 34.9 months), MFS (28.2 months vs 26.0 months), and LRFS (25.0 months vs 26.6 months). In particular, respective OS rates in the ENI and IFI groups were 84.6% and 82.5% after 1 year, 45.1% and 48.7% after 3 years, and 29.8% and 30.7% at 5 years. PFS rates after 1, 3, and 5 years were 58.9%, 34.2%, and 26.9%, respectively, in the ENI arm compared to 64.4%, 30.8%, and 27.7%, respectively, in the IFI arm. Multivariate analysis identified clinical stage and tumor responses as independent predictors of OS. Meanwhile, tumor location, cStage, and tumor response were identified as independent factors influencing PFS.ConclusionIFI was associated with similar survival as ENI in patients with thoracic ESCC, suggesting that IFI is an acceptable treatment method for thoracic ESCC.

Investigating the loco-regional control of simultaneous integrated boost intensity-modulated radiotherapy with different radiation fraction sizes for locally advanced non-small-cell lung cancer: clinical outcomes and the application of an extended LQ/TCP model

BackgroundTo investigate the loco-regional progression-free survival (LPFS) of intensity-modulated radiotherapy (IMRT) with different fraction sizes for locally advanced non-small-cell lung cancer (LANSCLC), and to apply a new radiobiological model for tumor control probability (TCP).MethodsOne hundred and three LANSCLC patients treated with concurrent radiochemotherapy were retrospectively analyzed. Factors potentially predictive of LPFS were assessed in the univariate and multivariate analysis. Patients were divided into group A (2.0 ≤ fraction size<2.2Gy), B (2.2 ≤ fraction size<2.5Gy), and C (2.5 ≤ fraction size≤3.1Gy) according to the tertiles of fraction size. A novel LQRG/TCP model, incorporating four “R”s of radiobiology and Gompertzian tumor growth, was developed to predict LPFS and compared with the classical LQ/TCP model.ResultsWith a median follow-up of 22.1 months, the median LPFS was 23.8 months. Fraction size was independently prognostic of LPFS. The median LPFS of group A, B and C was 13.8, 35.7 months and not reached, respectively. Using the new LQRG/TCP model, the average absolute and relative fitting errors for LPFS were 6.9 and 19.6% for group A, 5.5 and 8.8% for group B, 6.6 and 9.5% for group C, compared with 9.5 and 29.4% for group A, 16.6 and 36.7% for group B, 24.8 and 39.1% for group C using the conventional LQ/TCP model.ConclusionsHypo-fractionated IMRT could be an effective approach for dose intensification in LANSCLC. Compared with conventional LQ model, the LQRG model showed a better performance in predicting follow-up time dependent LPFS.

Last-line local treatment with the Quad Shot regimen for previously irradiated head and neck cancers

Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy. We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7Gy twice daily over 2 consecutive days at 4weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed. Median age was 66years. Median follow-up for all patients was 6.0months and 9.7months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were>2year interval from prior RT and 3-4 QS cycles. Median LPFS was 5.1months with 1-year LPFS 17.7%, and median OS was 6.4months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS>70, presence of palliative response and 3-4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n=18). No Grade 4-5 toxicities were observed. Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3-4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS>70 and proton therapy are associated with survival improvements.

Factors improving the outcome of patients re-irradiated with intensity-modulated radiotherapy (IMRT) for relapse or new head and neck cancer developed in irradiated areas.

Patients with secondary/recurrent squamous cell head and neck cancer have poor prognoses. Re-irradiation is a treatment option. However, best technique to re-irradiate is not known. This study aims to evaluate the outcome of patients treated with curative-intent intensity-modulated radiotherapy (IMRT) re-irradiation (re-RT) for head and neck (H&N) cancers. Fifty patients with recurrent H&N cancers underwent fractionated IMRT re-RT. The median time between the two courses of radiotherapy was 22 months. The median dose of re-RT was 66 Gy. The median follow-up of surviving patients was 13.6 months. The median overall survival (OS) was 15.7 months, and the 1- and 2-year OS rates were 62.4% and 33.9%, respectively. On multivariate analysis, performance status (PS) 0-1 (HR, 0.518; 95% CI: 0.292-0.917; P=0.024) and 3D-RT use during the first irradiation course technique (HR, 0.415; 95% CI: 0.183-0.938; P=0.035) were favorable, independent of significant prognostic factors of OS. The median loco-regional progression-free survival (LRPFS) was 8.3 months, and, the 1- and 2-year LRPFS rates were 46.6% and 35.9%, respectively. On multivariate analysis, a surgical resection before re-RT (HR, 0.107; 95% CI: 0.027-0.428; P=0.002), a higher age (HR, 0.894; 95% CI: 0.833-0.960; P=0.002), a PS 0-1 (HR, 0.316; 95% CI: 0.140-0.715; P=0.006), and a long re-RT interval (HR, 0.970; 95% CI: 0.945-0.996; P=0.024) were favorable independent significant prognostic factors of LRPFS. The median progression-free survival (PFS) was 7.0 months and, the 1- and 2-year PFS rates were 45.0% and 30.4%, respectively. On multivariate analysis, a surgical resection before re-RT (HR, 0.129; 95% CI: 0.036-0.466; P=0.002), a PS 0-1 (HR, 0.399; 95% CI: 0.208-0.764; P=0.006) and, a long re-RT interval (HR, 0.958; 95% CI: 0.927-0.989; P=0.009) were favorable, independent significant prognostic factors. The early and late toxicities rates were 28% and 34%, respectively. Re-RT for H&N cancers can be curative, and the complications can be manageable but patients need to be strictly selected. Surgery before re-RT could improve the patient outcome. Dose and irradiation schedules should be prospectively evaluated.

P2.17-25 Post-Treatment Neutrophil to Lymphocyte Ratio in Locally Advanced NSCLC Patients Treated with Concurrent Chemoradiotherapy

We aimed to investigate the relationship between NLR and prognosis in patients with locally advanced NSCLC who received concurrent chemoradiotherapy as the first line treatment. We retrospectively analyzed 62 patients with locally advanced NSCLC treated with definitive CCRT between 2008 and 2016 at Seoul St. Mary’s hospital. We excluded patients who received induction chemotherapy to eliminate their influence on NLR. CCRT consisted of weekly chemotherapy using paclitaxel/carboplatin, docetaxel/cisplatin, docetaxel/carboplatin, and etoposide/cisplatin. Radiotherapy was performed with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal RT (3D-CRT). The median radiation dose was 66 Gy in 33 fractions (range, 52 – 70 Gy). The pre-CCRT NLR was calculated from the nearest CBC within 1 week before CCRT and post-CCRT NLR was calculated using CBC 4 weeks after CCRT. Change of NLR before/after CCRT was also analyzed. The maximally selected log rank test was used to acquire the most significant NLR level related with overall survival (OS). The pre-, post-CCRT NLR, and NLR change (post-CCRT NLR/pre-CCRT NLR) cut-off levels were 1.9, 3.15, and 1.6, respectively. The median follow up duration was 11 months (range, 2–71 months). The 3-year OS, loco-regional progression free survival (LRPFS), and distant metastasis free survival (DMFS) were 45.4%, 9.3%, and 6.2%, respectively. The post-CCRT NLR and NLR change were significantly associated with OS and LRPFS. The high post-CCRT NLR group (> 3.15) showed significantly worse OS and LRPFS compared to the low post-CCRT NLR group (≤ 3.15) (3-year OS: 21.2% vs. 46.9%, p=0.005; median LRPFS: 7.7 months vs. 11.3 months, p=0.04). The high NLR change group (> 1.6) had significantly worse OS and LRPFS than the low NLR change group (≤ 1.6) (3-year OS: 32.7% vs. 36.9%, p=0.026; median LRPFS 7.7 months vs. 10.4 months, p=0.025). The pre-CCRT NLR showed a marginally significant difference in OS (3-year OS: 29.1% vs. 56.9%, p=0.062). There was no correlation between NLR and DMFS. The pre-, post-CCRT high NLR and increased NLR after CCRT are associated with poor prognosis of survival in patients for locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased risk of loco-regional failure. Further studies are needed to confirm the predictive value of NLR and the treatment strategies using NLR.

P1.17-02 Low Prognostic Nutritional Index Predicts Poor Survival in Stage IIIB Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy

The prognostic role of prognostic nutritional index (PNI) has been widely investigated and showed in many types of cancer. However, to our best knowledge, the significance of PNI has never been investigated in locally advanced non-small cell lung cancer (NSCLC) who were treated with concurrent chemoradiotherapy ( CCRT). Therefore in this current study, we aimed to investigate the prognostic impact of PNI on survival outcomes of locally advanced NSCLC undergoing CCRT. The data of 358 patients with stage IIIB NSCLC treated with CCRT were analyzed retrospectively. All patients received 60 to 66 Gy (2 Gy per fraction) thoracic radiotherapy and at least one course of platinum-based doublet chemotherapy concomitantly. For each patient PNI was calculated by the known formula in blood samples those were available prior to CCRT: [PNI=10×serum albumin (g/dl) + 0.005×total lymphocyte count (mm3)]. The primary endpoint was the association between PNI and overall survival (OS). Secondary endpoints were locoregional progression-free survival (LPFS) and progression-free survival (PFS). The survival curves were calculated by Kaplan-Meier method and log-rank test. The cutoff value of the PNI was analyzed by receiver operating curve (ROC). At a median follow-up of 22.5 months (2.4-123.5 months) 108 patients (30.2%) were still alive. For the whole study cohort median OS was 25.2 months (95 % CI: 22.7-27.7). The median LPFS and PFS were 15.4 months (95% CI: 14.4-16.4) and 10.7 months (95% CI: 9.7-11.7) respectively. In ROC analysis, calculated cutoff value of PNI was 40.1 (AUC: 67.8% (62.0-73.6); sensitivity: 73.1; specificity: 68.4, p<0.001). According to this, patients were grouped as follows, group 1: PNI>40 and group 2: PNI<40. Accordingly, for the patients in group 1, OS (36.7 vs. 16.8 months, p<0.001), LPFS (19.5 vs. 11.5 months, p<0.001) and PFS (13.6 vs. 8.6 months, p<0.001) times were significantly better as compared to patients in group 2. Results of the multivariate analysis demonstrated that the prognostic worth of PNI was independent of the other covariates (p<0.001, for each survival endpoints). Being the first of its kind study the result of this current investigation revealed that the PNI which is easy to calculate, easily achievable with no additional cost has a strong prognostic value in prognostic stratification of the stage IIIB NSCLC patients undergoing to CCRT.

Radiotherapy for patients with unresected locally advanced breast cancer.

Management of locally-advanced breast cancer is determined by multiple factors, but in patients without distant metastases often involves neoadjuvant systemic therapy, surgery and radiation. If the primary tumour remains unresectable following systemic therapy, radiotherapy may be used for tumour shrinkage prior to surgery. When metastatic disease is present, locoregional radiotherapy is generally reserved for management of tumour-related symptoms. We reviewed our experience of high-dose radiotherapy for unresected locally-advanced breast cancer. A retrospective chart review was conducted of patients with unresected locally advanced breast cancer (LABC) receiving external beam radiotherapy to the breast, chest wall and/or regional lymph nodes. Patients were stratified based on the presence of metastatic disease at presentation. Patient demographics, disease characteristics, and treatment outcomes were recorded. Forty-three cases were analyzed between 2004 and 2016. Median follow-up was 25 months from diagnosis and 14 months from completion of radiotherapy. There were 24 cases (56%) with metastatic disease on presentation, and 19 (44%) without. Tumour shrinkage occurred within 3 months of completing radiotherapy in 36 cases (84%). Ulceration and bleeding improved following radiotherapy in 13 (54%) of the 24 applicable cases. Twenty-six patients (60%) developed moist desquamation but none experienced grade 4 or 5 radiation dermatitis. Median locoregional progression-free survival for all patients was 12 months from completion of radiotherapy. Locoregional progression-free survival (P=0.2) and overall survival (OS) (P=0.4) were not significantly different between patients with and without distant metastases at presentation. Radiotherapy provided good response and symptom control in most patients in this study; there is a role for palliative radiotherapy in patients with LABC.

Genomic alterations and radioresistance in breast cancer: an analysis of the ProfiLER protocol

BackgroundBreast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, party related to a possible radiotherapy resistance leading to local-regional recurrences (LRR). The objective of the present study was to identify predictive molecular biomarkers of LRR of BC. Patients and methodsGenetic profile of 146 BC patients’ tumours included in the ProfiLER clinical trial (NC01774409) between 2013 and 2016 were analysed using next-generation-sequencing and comparative-genomic-hybridization tests. Patients and tumour characteristics were retrospectively collected and analysed for association with genomic rearrangements (mutations, amplification, deletions). Only gene alterations observed in>3% of the tumours were selected. ResultsA total of 193 genomic rearrangements were identified, and 16 were observed in>3% of tumours. One was statistically correlated to the risk of local relapse. A median loco-regional progression-free survival (LRPFS) of 23.6years was reported for PIK3CA mutation carriers (n=31, 21.2%) versus 9.9years for PIK3CA wild-type patients (HR 0.27, 95% CI 0.12–0.65, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor on LRR using multivariate analysis (HR 0.29, 95% CI 0.09–0.99, P = 0.047). All other mutations, amplifications or deletions were not found associated with LRPFS. ConclusionPIK3CA mutation was associated with a lower risk of local relapse in this population of BCs. This is consistent with recent studies suggesting PIK3CA to be part of biological pathways impacting the radiosensitivity.

Genomic Alterations and Radioresistance in Breast Cancer: An Analysis of the Profiler Protocol

Purpose/Objective(s) Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, partly because of radiotherapy resistance leading to loco-regional recurrences (LRR). The ProfiLER (Profilage LYric et Region, NCT01774409) clinical trial aims at establishing a simple genetic profile of metastatic cancers in order to offer patients personalized molecular targeted therapies. In the breast cancer area, the genomic profiling of a population who ultimately became metastatic, and its correlation with the patient outcome years after LRR, provided an opportunity to identify post hoc biomarkers of the initial radiation resistance. The aim of the present study was to determine if specific tumor genetic alterations were associated with radiation resistance, defined as a LRR despite optimal surgery, radiotherapy, and systemic adjuvant therapies, in a ProfiLER series. Materials/Methods Genetic profile of 162 BC patients’ tumors included in ProfiLER between 2013 and 2016 were analyzed using Next-Generation-Sequencing and Comparative-Genomic-Hybridization tests. Patients and tumor characteristics were analyzed for association with genomic rearrangements (mutations, amplification, homozygous deletions). Only gene alterations observed in >3% of the tumors, or included in well-known molecular pathways (PI3 Kinases pathway, MAP Kinases pathway, Tyrosine Kinase receptors family) were selected. The Cox multivariate analysis was based on (P<0.2)-factors in univariate analysis. Results Two hundred eighteen genomic rearrangements were identified, and 18 were observed in >3% of tumors. PIK3CA and ROS1 mutations were statistically correlated to the risk of LRR. A median loco-regional progression free survival (LRPFS) of 19.8 years was reported for PIK3CA mutation carriers (n = 34, 21%) versus 9.1 years for wild-type patients (HR = 0.29, 95% CI = 0.13-0.64, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor of LRR using multivariate analysis (HR = 0.27, 95% CI = 0.09-0.82), P = 0.02). ROS1 mutated cancer patients (n = 8, 4.9%) had a median LRPFS of 4 years versus 16.1 years for wild-type patients (HR = 2.5, 95% CI = 1.74-7.05, P = 0.08 in univariate analysis), but was not identified as an independent LRR risk factor (HR = 2.45 95% CI = 0.83-7.26, P = 0.11 in multivariate analysis). Other mutations and amplifications were not associated with LRR. Among relapsing patients, the median time to LRR was nearly significantly different regarding status of the PIK3CA mutations, with 8.6 years for mutated patients versus4.7 years for non-mutated patients (P = 0.09). Conclusion PIK3CA mutation was associated with a lower risk of LRR in this BC population. ROS1 mutation was marginally associated with a higher risk of LRR, possibly because of a limited population. Results suggest PIK3CA and ROS1to be possible biomarkers of radio-sensitivity.

Efficacy of isolated limb perfusion (ILP) in patients with Merkel cell carcinoma (MCC): A multicenter experience

BackgroundMerkel cell carcinoma (MCC) is a rare and potentially aggressive neuroendocrine tumor of the skin, with a propensity for locoregional metastases. In two expert referral centers, isolated limb perfusion (ILP) is used to obtain locoregional control in selected locoregionally advanced MCC patients. This study describes our experience. MethodPatients who underwent ILP for MCC were analyzed. ILP was performed with melphalan and tumor necrosis factor (TNF) combination therapy. Depending on the institution, either a normothermic or a hyperthermic temperature regimen was used. Baseline characteristics, toxicity data, locoregional progression-free survival (LPFS) and overall survival (OS) were assessed. ResultsFour males and 6 females with a median age of 78 years (IQR 61–84 years) were included. Four patients underwent ILP for upper extremity disease and 6 for lower extremity disease. All patients received combination therapy with Melphalan and TNF, one patient with the addition of interferon-gamma. No signs of systemic toxicity were present post-ILP. Severe locoregional toxicity (compartment syndrome) occurred in 1 patient and 1 elderly patient with extensive atherosclerosis had to undergo transfemoral amputation due to critical ischemia. Eight patients could be included for response evaluation. The overall response rate (ORR) was 87.5% with a complete response (CR) rate of 62.5%. Two long-term responses of 53 months and 71 months were observed. Median LPFS was 5 months and median OS was 54 months. ConclusionILP shows a high CR rate that can be durable. Therefore, ILP should be considered an effective treatment modality for locally advanced MCC.

Isolated Limb Perfusion for Melanoma is Safe and Effective in Elderly Patients

Data on isolated limb perfusion (ILP) in elderly melanoma patients are scarce. We aimed to evaluate the efficacy and safety of ILP in our institutional cohort of melanoma patients. We performed retrospective analysis of stage IIIB/C melanoma patients who underwent ILP for melanoma in-transit metastases (ITMs) in our institution between 2000 and 2016. Normothermic ILP was performed with either melphalan or melphalan and tumor necrosis factor. Baseline and treatment characteristics, locoregional progression-free survival (LPFS) and melanoma-specific survival (MSS) were assessed and prognostic factors for response, recurrence, and survival were analyzed using univariable and multivariable analysis. Overall, 91 patients were included in this study. Based on the median age of 70years, we split patients into younger and elderly groups. No differences in response rates were observed between age groups, with an overall response rate of 81% and complete response (CR) rate of 47%. LPFS did not differ between age groups, and median LPFS was 16months for patients with a CR. Median MSS was 38months and differed between younger (45months) and elderly patients (18months). Toxicity was generally mild and did not differ between age groups. Two patients (2.2%) suffered Wieberdink IV toxicity, while no patients required amputation because of severe toxicity. CR was prognostic for improved LPFS and MSS, while patients >70years of age and patients with stage IIIC disease had a higher risk of melanoma-specific death. Because of its safety profile and high CR rates, ILP is a viable option for patients with bulky or multiple melanoma ITMs, including elderly (>70years of age) patients.