OUTCOME OF PATIENTS TREATED WITH BLADDER PRESERVATION PROTOCOL IN UROTHELIAL CARCINOMA OF URINARY BLADDER

Objective: To explore trimodality treatment with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy as an alternative approach to neoadjuvant chemotherapy followed by radical cystectomy, for the treatment of non-metastatic muscle invasive bladder carcinoma. Study Design: Retrospective observational study. Place and Duration of Study: Combined Military Hospital Rawalpindi Pakistan, from 2006 and 2015. Methodology: A total of 122 patients were evaluated in a retrospective manner. Primary endpoint was overall survival. Patients received four courses of neoadjuvant chemotherapy followed by radical concurrent chemoradiotherapy with Cisplatin as radiation sensitizer. Result: 5-year overall survival was 80 (66%) in this population and a complete response following completion of treatment was seen in 93 (76.3%) patients. Subset analysis showed markedly increased 5-year overall survival of around 104 (85%) in patients having complete response after neoadjuvant chemotherapy. Conclusion: The study concludes that bladder preservation is an acceptable alternative to radical cystectomy in selected population especially among those who had a complete response to the initial four courses of chemotherapy.

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.

RADT-22. CONCURRENT TTFIELDS (200 KHZ) WITH CHEMORADIATION FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF PSEUDOPROGRESSION: ANALYSIS OF A PILOT CLINICAL TRIAL

OBJECTIVE The standard of care for the adjuvant treatment of glioblastoma is concurrent chemoradiation, maintenance temozolomide, and Tumor Treating Fields (TTFields). TTFields may reversibly impact the blood-brain barrier, most significantly at 100 kHz. We hypothesized that this may increase the rate of pseudoprogression (PsP) in patients who receive concurrent chemoradiation with TTFields (200 kHz). METHODS This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Patients with newly diagnosed glioblastoma, age ≥ 18 years, and KPS ≥ 60 were eligible. They received concurrent temozolomide (75 mg/m2), scalp-sparing radiation (60 Gy in 30 fractions), and TTFields (200 kHz). Radiation was delivered through the TTFields arrays. PsP was defined as radiographic progression of enhancing lesions without clinical decline that improved or remained stable upon subsequent imaging. The rate of PsP was determined by an evaluation of the 2nd MRI at our multidisciplinary tumor board after the completion of trimodality treatment. These findings were confirmed with official radiology reports. RESULTS 30 patients were enrolled. Of these, 29 had imaging available for evaluation. Male-to-female ratio was 20:10. Median follow-up was 11.6 months (1.6-22.4 months), median age was 58 years (19-77 years), and median KPS was 90 (70-100). 20 (66.7%) patients had unmethylated and 10 (33.3%) had methylated MGMT promotor. Median time from surgery to initiation of radiation was 34 days (26-49 days). Median time from completion of trimodality treatment to 2nd follow-up MRI was 90 days (29-109 days). 15/29 (51.7%) patients had PsP. Patients with methylated and unmethylated MGMT promotor had 50.0% (5/10) and 52.6% (10/19) rates of progression respectively. CONCLUSIONS 51.7% of the patients who received concurrent chemoradiation with TTFields demonstrated PsP. The incidence is greater than historical reports. However, these findings should be explored in larger cohorts as this study was limited by a small sample size.

Correlation of clinical characteristics and immunologic profile of stage III NSCLC patients.

e20552 Background: Recently, immunotherapy has significantly increased mPFS and mOS in unresectable stage III NSCLC whom completed concurrent chemoradiation (CCRT). Predictive biomarker for immunotherapy in this setting has not been established yet. Methods: This is a retrospective study in stage III NSCLC patients in Ramathibodi hospital between year of 2013 and 2019. Clinical data of 176 patients were retrieved from electronic medical record. Only 64 patients had adequate tissue for tissue array for immunohistochemistry (IHC) staining of protein expression in CD3, CD4, CD8, FOXP3, PDL-1, CD163, CD 138, CD20 in stroma and tumor cells. We also performed IHC staining for Microsatellite Instability (MSI). Optimum cut point for each protein expression was performed by C-statistic. Survival analysis was performed. All statistical analysis was performed by Stata version 15. Results: Of 176 patients, majority of patient were male (63.6%), age ≥65 years (63.6%), never-smoker (40.9%), stage IIIB (44.9%) and adenocarcinoma (67.6%). EGFR-positive patients were 47.7%. Most of the patients underwent CCRT (32.4%), only 11.9% underwent trimodality treatment. Doublet-carboplatin based chemotherapy was the most common regimen (61.5%). The mOS was 2.9 years and mPFS was 1.6 years. Multivariable analysis showed stage IIIB patients, patients whom received only systemic treatment or best palliative care had significantly shorter OS. Trimodality treatment showed significantly longer OS compared to bimodality (CCRT) (HR = 0.18, P= 0.02), as well as cisplatin-based chemotherapy had significantly longer OS compared to carboplatin-based regimen (HR = 0.47, P= 0.005). Of 64 patients whom had tissue testing in our study, majority of patients had of MSI-low (81.25%), PD-L1 negative (78.13%). Regarding tumor microenvironment, patients with high protein expression of CD3, CD4, CD8 and CD20 in stromal cells showed significantly longer OS, whereas MSI and PD-L1 were not significantly associated with survival outcomes. Conclusions: OS in stage III NSCLC in our population (2.9 years) is comparable with other studies (2.4 years). Trimodalities treatment significantly increased OS compared to CCRT. High protein expression of CD3, CD4, CD8 and CD20 in stroma probably potential prognostic and predictive biomarkers for immunotherapy in stage III NSCLC. Larger cohort is needed to explore.

The rate and risk of secondary pelvic malignancies (SPM) in patients treated with definitive radiation for locally advanced rectal cancer.

12065 Background: With a rising incidence of younger patients diagnosed with rectal cancer, the long-term toxicity of cancer-related therapy is becoming even more relevant. Risk of SPM is a known potential consequence of both chemotherapy (chemo) and radiation therapy (RT), yet the rate of SPM in patients with rectal cancer is still not defined. We sought to further investigate factors associated with and outcomes of SPM after RT for rectal cancer. Methods: Patients diagnosed with stage II-III rectal cancer treated with chemo and/or RT from 1995-2019 were included in a retrospective study. Patients treated with palliative intent and those who survived < 5 years from treatment were excluded. RT-associated SPM was defined as a cancer occurring ³5 years after RT completion. Cumulative incidence (CI) of SPM was analyzed using a landmark analysis at 5 years with death as a competing risk. For patients with CT simulation scans available, dosimetric analyses evaluated doses to the organs developing SPM. Kaplan Meier analysis was used to evaluate overall survival among patients who developed an SPM. Results: A total of 2,700 patients were included (RT = 978; chemo = 1722). Demographic characteristics were equivalent apart from age, which was higher in the RT group (61 vs 59 years, p < 0.001). Five (0.3%) chemo patients developed an SPM, all within 5-10 years after treatment for rectal cancer, vs 48 (4.9%) RT patients. The 8-year CI of developing an SPM in the RT group was 4% (95% CI 2.4-6.2) and increased to 17% at 15 years (95% CI 12.1-21.8) and 21% at 20 years (95% CI 14.8-27.7). Most (89%) RT patients had received chemotherapy (most commonly 5-FU or FOLFOX). The median time to SPM was 108 months (interquartile range [IQR], 84-140). After pelvic RT, the most common SPM histology was endometrial (38%), followed by prostate (31%), bladder (23%), sarcoma (4.2%), and other gynecologic cancers (4.2%). Seven patients had CT simulations for dosimetric analyses: median of maximum dose to the organ with SPM was 5301cGy (IQR, 4928-5427), median of mean dose was 4551 cGy (IQR, 4476-4751). None of the patients who developed endometrial cancer had Lynch syndrome. Median OS for patients with SPM after RT was 5.1 years with 5-yr OS of 58% (95% CI 43-77); 44 out of 48 patients needed at least one treatment modality for their SPM, and 8 received trimodality treatment [surgery, chemo and RT]. Conclusions: The CI of SPM increased from 4% at 8 years to 17% at 15 years and 21% at 20 years following pelvic RT for rectal cancer. Endometrial cancer was the most common SPM and survival following treatment of SPM was favorable. These data serve as a foundation for future prospective studies evaluating ways to reduce SPM such as proton therapy.