Az osztott dózisú trimodális kezelés első hazai alkalmazása nagy kockázatú húgyhólyagdaganat esetében

Összefoglaló. Az izominvazív vagy nagyon nagy kockázatú, felületes hólyagdaganatok kezelésének arany standardja a radikális húgyhólyag-eltávolítás (cystectomia). Válogatott betegek esetében hasonló hatékonyságú kezelés lehet az osztott dózisú (split-course) trimodális terápia, az endoszkópos tumorreszekció és a kemoirradiáció megszakított ciklusokkal történő alkalmazása. A split-course trimodális terápia a radikális cystectomiához hasonló eredményességű, a későbbi életminőség szempontjából pedig ígéretes kezelési lehetőség lehet megfelelően kiválasztott betegek esetében. Hazánkban első alkalommal végzett kezelést ismertetünk a téma szakirodalmi áttekintése mellett. A húgyhólyagtumor transurethralis reszekciója, maximális eradikációja után kemoirradiáció kezdődik, melyet 45 Gy sugárdózis elérésekor ismételt szövettani mintavétel szakít meg. Negatív szövettani eredmény esetén a megkezdett terápia a teljes dózis eléréséig folytatandó. Amennyiben a reszekció során élő tumor észlelhető, a radikális műtét elvégzése javasolt. A korábban transurethralis daganatreszekción négyszer átesett 54 éves beteg lokális immunterápia utáni recidívájának szövettana pT1, ’high grade’ urothelialis carcinoma volt. A jól informált, kiváló fizikális statusú beteg kérését figyelembe véve split-course trimodális kezelést végeztünk. Negatív ’staging’ vizsgálatok után maximális endoszkópos reszekció, majd kemoirradiáció következett. A 45 Gy besugárzás elérésekor elvégzett ismételt mintavétel azonnal feldolgozott szövettana negatív eredményt mutatott, így késedelem nélkül folytatódott a kemoirradiációs kezelés. Az eddigi kontrollvizsgálatok alapján a beteg komplett remisszióban van. A split-course trimodális terápia a radikális hólyageltávolítás megfelelő alternatívája jól informált, gondosan megválogatott betegek esetében. A szervmegtartó eljárás jobb életminőséget eredményezhet, ugyanakkor a beteget feltétlenül tájékoztatni kell, hogy sikertelenség esetén a radikális műtét is szükségessé válhat. A kezelés sikeres menedzselése csak a társszakmák szoros, jól tervezett együttműködésével lehetséges. Orv Hetil. 2021; 162(50): 2017–2022. Summary. While radical cystectomy remains the gold standard to treat muscle-invasive or very high risk superficial bladder cancer, well selected patients can be offered split-course multimodal treatment as a similarly effective alternative, combining endoscopic tumor resection and split-course chemoradiotherapy. In highly selected patients, split-course trimodality therapy can lead to survival rates comparable to radical cystectomy with better quality of life outcomes. We present our experience with split-course trimodality treatment used for the very first time in Hungary. Maximal transurethral resection of bladder neoplasm is followed by chemoradiotherapy with repeated bladder biopsy after 45 Gy of irradiation. With negative biopsy results, chemoirradiation should be continued until full dose given. Salvage cystectomy is recommended if viable tumor is detected. Our patient (54), who previously underwent four transurethral bladder tumor resections and local immunotherapy, presented with pT1, high grade urothelial carcinoma recurrence. The well-informed, high performance status patient opted for split-course trimodality treatment. After negative staging scan results, the patient underwent complete endoscopic tumor eradication, followed by chemoradiotherapy. After 45 Gy of irradiation, repeated bladder biopsy was performed. The immediate histopathological examination found no viable tumor, therefore chemoradiotherapy was completed. Follow-up examinations suggest our patient in complete remission. Split-course trimodality treatment can be offered to well-informed and selected patients as a reasonable alternative to radical cystectomy. Though the bladder-sparing approach results in better quality of life, patients must know that in the case of treatment failure, radical cystectomy will likely be offered. Excellent multidisciplinary cooperation is a key to conduct this treatment alternative successfully. Orv Hetil. 2021; 162(50): 2017–2022.

Comparative analysis of long-term oncologic outcomes for minimally invasive and open Ivor Lewis esophagectomy after neoadjuvant chemoradiation: a propensity score matched observational study

Background Locally advanced esophageal carcinoma is typically treated with neoadjuvant chemoradiation and esophagectomy (trimodality therapy). We compared the long-term oncologic outcomes of minimally invasive Ivor Lewis esophagectomy (M-ILE) cohort with a propensity score weighted cohort of open Ivor Lewis esophagectomy (O-ILE) cases after trimodality therapy. Methods This is a retrospective review of 223 patients diagnosed with esophageal carcinoma who underwent neoadjuvant chemoradiation followed by M-ILE or O-ILE from April 2009 to February 2019. Inverse probability of treatment weighting (IPTW) adjustment was used to balance the baseline characteristics between study groups. Kaplan–Meier survival curves were calculated for overall survival and recurrence-free survival comparing the two groups. Multivariate Cox proportional hazards regression models were used to determine predictive variables for overall and recurrence-free survival. Results The IPTW cohort included patients with esophageal carcinoma who underwent M-ILE (n = 142) or O-ILE (n = 68). The overall rate of postoperative adverse events was not significantly different after IPTW adjustment between the O-ILE and M-ILE trimodality groups (53.4% vs. 39.2%, p = 0.089). The 3-year overall survival (OS) for the M-ILE group was 59.4% (95% CI: 49.8–67.8) compared to 55.7% (95% CI: 39.2–69.4) for the O-ILE group (p = 0.670). The 3-year recurrence-free survival for the M-ILE group was 59.9% (95% CI: 50.2–68.2) compared to 61.6% (95% CI: 41.9–76.3) for the O-ILE group (p = 0.357). A complete response to neoadjuvant chemoradiation was significantly predictive of improved OS and RFS. Conclusion The overall and recurrence-free survival rates for M-ILE were not significantly different from O-ILE for esophageal carcinoma after trimodality therapy. Complete response to neoadjuvant chemoradiation was predictive of improved overall and recurrence- free survival.

The Prognostic Role of Blood Inflammatory Biomarkers and EGFR Mutation Status in Stage IIIA/N2 Non-Small Cell Lung Cancer Patients Treated With Trimodality Therapy

ObjectivesVarious blood inflammatory biomarkers were associated with treatment response and prognosis of non-small cell lung cancer (NSCLC) in previous studies. In this study, we retrospectively evaluated the prognostic role of pretreatment blood inflammatory biomarkers and epidermal growth factor receptor (EGFR) mutation status in stage IIIA/N2 NSCLC patients with trimodality therapy.MethodsCompletely resected stage IIIA/N2 NSCLC patients with adjuvant chemotherapy and postoperative radiotherapy (PORT) were assessed in this study. Cutoff values of blood inflammatory factors were calculated by the R package SurvivalROC of R software. SPSS Statistics software was used for survival analyses. Kaplan-Meier survival curve and log-rank test were used to compare the survival difference between every two groups. Univariate and multivariate analyses of predictive factors were performed by Cox proportional hazards regression model.ResultsThe univariate analysis showed that T stage (p=0.007), EGFR mutation status (p=0.043), lymphocyte-to-monocyte ratio (LMR) (p=0.067), and systemic immune-inflammation index (SII) (p=0.043) were significant prognostic factors of disease-free survival (DFS). In the multivariate analysis, T2 (HR=0. 885, 95% CI: 0.059-0.583, p=0.004), EGFR mutation-positive (HR=0.108, 95% CI: 0.023-0.498, p=0.004) and elevated pretreatment SII (HR=0.181, 95%CI: 0.046-0.709, p=0.014) were independently related to shorter DFS. High pretreatment neutrophil counts (HR=0.113, p=0.019) and high systemic inflammation response index (SIRI) (HR=0.123, p=0.025) were correlated with worse overall survival (OS) by the univariate analysis. In the multivariate analysis, only high pretreatment SIRI was an independent predictor for poorer OS (HR=0.025, 95% CI: 0.001-0.467, p=0.014).ConclusionsIn conclusion, we identified that high pretreatment SII and SIRI were unfavorable prognostic factors in stage IIIA/N2 NSCLC patients treated with surgery, adjuvant chemotherapy and PORT. Patients with high pretreatment SII, high pretreatment SIRI, T2, and EGFR mutation-positive may need more forceful adjuvant treatment. Further prospective studies with large-scale are needed to validate our results and identify the proper cut-off values and optimum adjuvant treatment for distinct patient population.

Systemic Immune-Inflammatory Index Association with Survival in Patients Undergoing Trimodality Therapy for Lung Cancer

Purpose: The systemic immune-inflammation index (SII) is correlated with patient survival in various solid malignancies including non-small cell lung cancer (NSCLC). However, limited information is available on the prognostic implication of SII in patients undergoing trimodality therapy for stage III Non-Small Cell Lung Carcinoma (NSCLC). Methods: At our institution, 81 patients underwent curative intent trimodality therapy (neoadjuvant chemoradiotherapy followed by surgical resection) for stage III NSCLC from 2004-2019. SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. Chi-squared analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate disease free survival (DFS), overall survival (OS), and freedom from recurrence (FFR) rates, with Cox regression used to determine absolute hazards. Results: Patients underwent neoadjuvant radiation therapy to a median dose of 4500 cGy concurrent with a median of 3 cycles of chemotherapy (most commonly carboplatin and paclitaxel) followed by surgical resection (86.4% lobectomy and 13.6% pneumonectomy) with mediastinal lymph node dissection. At a median follow-up of 68.4 months, a low SII (<1260) at diagnosis was independently associated with an improved OS (HR: 0.448, p=0.004), DFS (HR: 0.366, p<0.001), and FFR (HR: 0.325, p=0.002). Conclusions: We identified that a low SII was associated with improved OS, DFS, and FFR in patients undergoing trimodality therapy for stage III NSCLC. The interplay of the immune system and lung cancer outcomes remains an active area of investigation for which further study is warranted.