Complete Response Patients Research Articles

CAR-T Cells and Oncolytic Viruses: Joining Forces to Overcome the Solid Tumor Challenge.

Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells has resulted in unprecedented rates of long-lasting complete responses in patients with leukemia and lymphoma. However, despite the impressive results in patients with hematologic malignancies, CAR-T cells have showed limited effect against solid cancers. New approaches will need to simultaneously overcome the multiple challenges that CAR-T cells encounter in solid tumors, including the immunosuppressive tumor microenvironment and heterogeneity of antigen expression. Oncolytic viruses are lytic and immunogenic anti-cancer agents with the potential to synergize with CAR-T cells for the treatment of solid tumors. In addition, viruses can be further modified to deliver therapeutic transgenes selectively to the tumor microenvironment, which could enhance the effector functions of tumor-specific T cells. This review summarizes the major limitations of CAR-T cells in solid tumors and discusses the potential role for oncolytic viruses as partners for CAR-T cells in the fight against cancer.

Impact of Chemoradiotherapy Intensity on Pathological Complete Response in Patients with Esophageal Cancer Receiving Trimodality Therapy

Despite the current standard of neoadjuvant chemoradiation therapy followed by radical surgery improving outcomes in patients with operable esophageal carcinoma (EC), there are still limited reports of clinical and treatment-related features that might predict pathological complete response (pathCR), which indicated superior survival outcome in many series. The purpose of this study is to evaluate if chemoradiotherapy intensity and other clinical or treatment-related features might predict pathCR and acute toxicity in patients with esophageal cancer who received trimodality therapy. We retrospectively analyzed clinical and treatment-related features of 127 consecutive patients with EC who received trimodality therapy in two tertiary centers between January 2010 and December 2015. Either primary or nodal specimens with no residual carcinoma were defined as pathCR. We applied logistic regressions to identify independent clinical or treatment related features, especially chemoradiotherapy intensity, associated with pathCR and acute toxicity. The receiver-operating characteristic (ROC) curve was also generated to obtain the best cut-off point. With a majority of squamous cell histology (N=124, 97.6%) and male gender (N= 121, 95.3%), all patients received neoadjuvant therapy with cisplatin and fluorouracil chemotherapy and radiotherapy. A pathCR was achieved in 47 (37%) of 127 patients. Low-grade tumors (odds ratio [OR]: 32.279; p < .0001) and cumulative cisplatin dose (mg/m2) during radiotherapy (OR: 1.031; p < .0001, cut-off point: 128.5 mg/m2) significantly predicted higher pathCR rates in multivariate logistic regression models. A lower pathCR rate was observed in patients with greater body weight loss (by percentage) during neoadjuvant therapy (OR: 0.865, p= .010, cut-off point: 8.85%). Meanwhile, the higher radiation dose to gross tumors was not associated with pathCR (OR: 1.000, p= .374), but was the only independent factor that significantly predicted severe (≥ grade 3) acute hematologic toxicity (OR: 1.002, p< .001, cut-off point: 5200 cGy). Low-grade tumors and cumulative cisplatin dose during radiotherapy were predictive of a higher possibility of pathCR. Greater body weight lost during neoadjuvant therapy was a negative predictor for pathCR. Increasing radiation dose did not contribute to pathCR, but did increase the severity of acute hematologic toxicity. Interventions that improve treatment tolerance as per protocol and nutrition status during neoadjuvant therapy are needed to achieve higher pathCR rates and potentially better outcomes.

633P - The role of comprehensive evaluation for clinical complete response in predicting pathologic complete response in patients treated with neoadjuvant chemoradiation for esophageal squamous cell carcinoma (ESCC)

633P - The role of comprehensive evaluation for clinical complete response in predicting pathologic complete response in patients treated with neoadjuvant chemoradiation for esophageal squamous cell carcinoma (ESCC)

The Utility of Pretreatment and Posttreatment Lymphopenia in Cervical Squamous Cell Carcinoma Patients Treated With Definitive Chemoradiotherapy.

The aim of this study was to investigate the prognostic significance of pretreatment and posttreatment lymphopenia in locally advanced squamous cell carcinoma (SCC) cervical cancer patients treated with definitive chemoradiotherapy (ChRT). Data from 95 patients with SCC were retrospectively analyzed. Relationships between pretreatment or posttreatment lymphopenia and patient or tumor characteristics, and overall survival (OS) and disease-free survival (DFS) were evaluated. Median follow-ups for the entire cohort and survivors were 68 months (range, 3-133 months) and 88 months (range, 22-133 months), respectively. Ten patients (11%) exhibited pretreatment lymphopenia, whereas 58 patients (61%) exhibited posttreatment lymphopenia. Median pretreatment total lymphocyte counts decreased from 2029 cells/μL to 506 cells/μL 2 months after ChRT (P < 0.001). The 5-year OS and DFS rates were significantly higher in patients without pretreatment lymphopenia compared with patients with pre-retreatment lymphopenia (61% vs 20% [P < 0.001], 55% vs 20% [P < 0.001]). Patients without posttreatment lymphopenia had significantly higher 5-year OS and DFS rates than their counterparts (70% vs 46% [P = 0.02], 70% vs 39% [P = 0.004]). Complete response (CR) was observed in significantly fewer patients with pretreatment lymphopenia than in those without, after ChRT. Patients with posttreatment lymphopenia had higher rates of lymph node metastasis (P = 0.001) and lower posttreatment CR rates (P = 0.01) versus patients without posttreatment lymphopenia. In univariate analysis, International Federation of Gynecology and Obstetrics stage, tumor size, lymph node metastasis, and treatment response were prognostic for OS and DFS. In multivariate analysis, pretreatment lymphopenia, lymph node metastasis, and treatment response were independent predictors of OS and DFS. Age was predictive of OS. Tumor size was prognostic for DFS. Pretreatment lymphopenia and posttreatment lymphopenia are associated with worse treatment response in patients given ChRT for cervical SCC. Pretreatment lymphopenia is predictive for OS and DFS. Therapeutic strategies including pretreatment or posttreatment immune preservation or modulation may improve response rates and survival in women with cervical SCC.

Application of intravoxel incoherent motion sequence in evaluating and predicting response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma

Objective To assess intravoxel incoherent motion(IVIM) in evaluating and predicting response to neoadjuvant chemotherapy(NAC) in esophageal squamous cell carcinoma(ESCC). Methods Forty-seven patients with ESCC diagnosed by pathological findings on biopsy from September 2015 to March 2017 were prospectively collected. All patients were examined before and after NAC using routine MRI scan and IVIM. The standard apparent diffusion coefficient (ADCstandard), diffusion coefficient (D), perfusion coefficient (D*) and perfusion score (f) were measured. The patients were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) according to the 1.1 version of the response evaluation criteria in solid tumors (RECIST). Thirty-one patients underwent surgery after NAC, and the patients were divided into TRG 0-3 according to tumor regression grade (TRG). The differences of parameter values before and after NAC between different groups were analyzed using Student's t test (normal distribution) and Wilcoxon rank sum tests (non-normal distribution). The parameters with statistical significance were evaluated by the receiver operating characteristics (ROC) curves. Results The ADCstandard values before and after NAC were (1.97±0.51) ×10-3, (2.42±0.52)×10-3 mm2/s. The D values before and after NAC were (1.30±0.30)×10-3, (1.63±0.35)×10-3 mm2/s. The ADCstandard and D values after NAC were significantly higher than those before NAC, and the differences were statistically significant (t=-6.35, -5.25 respectively, both P 0.05). The patients were divided into PR group (29 cases) and SD group (18 cases) after NAC, without CR and PD patients. The ADCstandard, D and f values of PR group were significantly lower than those of the SD group before NAC (t=-3.11, -2.53 and -2.10 respectively, all P<0.05). The ADCstandard, D, D* and f values after NAC revealed no significant difference between PR and SD groups. Thirty-one patients received operation after NAC, which were divided into TRG 2 group (14 cases) and TRG 3 group (17 cases) according to TRG standard, without TRG 0 and TRG 1 patients. All the parameter values before NAC revealed no significant difference between TRG 2 and TRG 3 groups. The D values after NAC in TRG 2 and TRG 3 groups were (1.81±0.31)×10-3, (1.46±0.39)×10-3 mm2/s respectively, and the significant difference was found between two groups (t=2.76, P<0.05). The efficiency of efficacy evaluation for NAC was the highest at D value of 1.68×10-3 mm2/s, with sensitivity and specificity being 85.7% and 70.6%, respectively. Conclusion IVIM can be used as a new imaging method to evaluate and predict the efficacy of NAC for ESCC, among which the parameter D was the most valuable. Key words: Esophageal neoplasms; Magnetic resonance imaging; Intravoxel incoherent motion; Neoadjuvant chemotherapy

Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis.

Incomplete peripheral blood B cell depletion after rituximab in lupus nephritis might correlate with inability to reduce tubulointerstitial lymphoid aggregates in the kidney, which together could be responsible for inadequate response to treatment. We utilized data from the Lupus Nephritis Assessment with Rituximab (LUNAR) study to characterize the variability of peripheral blood B cell depletion after rituximab and assess its association with complete response in patients with lupus nephritis. We analyzed 68 participants treated with rituximab. Peripheral blood B cell depletion was defined as 0 cells/µl, termed "complete peripheral depletion," assessed over 78 weeks. Logistic regression was used to estimate the association between characteristics of complete peripheral depletion and complete response (defined as urine protein-to-creatinine ratio <0.5 mg/mg, and normal serum creatinine or an increase in creatinine <15%, if normal at baseline), assessed at week 78. A total of 53 (78%) participants achieved complete peripheral depletion (0 cells/µl) in a median time of 182 days (interquartile range, 80-339).The median duration of complete peripheral depletion was 71 days (interquartile range, 14-158). Twenty-five (47%) participants with complete peripheral depletion achieved complete response, compared with two (13%) without. Complete peripheral depletion was associated with complete response (unadjusted odds ratio [OR], 5.8; 95% confidence interval [95% CI], 1.2 to 28; P=0.03). Longer time to achieving complete peripheral depletion was associated with a lower likelihood of complete response (unadjusted OR, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Complete peripheral depletion lasting >71 days (the median) was associated with complete response (unadjusted OR, 4.1; 95% CI, 1.5 to 11; P=0.008). There was substantial variability in peripheral blood B cell depletion in patients with lupus nephritis treated with rituximab from the LUNAR trial. Achievement of complete peripheral depletion, as well as the rapidity and duration of complete peripheral depletion, were associated with complete response at week 78. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_06_CJASNPodcast_18_10_.mp3.

A systematic review and meta-analysis of treatment for hepatorenal syndrome with traditional Chinese medicine.

Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver diseases. It has been reported that traditional Chinese medicine (TCM) may improve liver function, delay disease progression, alleviate symptoms, and improve quality of life in HRS patients. The study aims to systematically review the efficacy of TCM for the treatment of HRS. Publications were searched electronically from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, and EMBASE databases. Odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed. The Cochrane Collaboration's tool was used to assess the risk of bias. Fourteen randomized controlled trials involving 788 patients with HRS were included. Random generation sequence was reported in only two studies. Blinding was not used in any study. Compared to conventional treatment without TCM, TCM led to a significant survival benefit during hospitalization (OR: 0.18; 95% CI: 0.08-0.39; P<0.0001), a significantly higher complete response (OR: 3.20; 95% CI: 2.06-4.97; P<0.00001), and a significantly lower no response (OR: 0.20; 95% CI: 0.14-0.30; P<0.00001). Partial response was not significantly different between the two groups (OR: 1.39; 95% CI: 0.90-2.15; P=0.14). Regardless of TCM, blood urea nitrogen and abdominal circumference were significantly decreased, and urine volume was significantly increased after treatment. Compared to conventional treatment without TCM, TCM led to a significantly lower serum creatinine, blood urea nitrogen, bilirubin, plasma ammonia, and abdominal circumference and significantly higher urine volume after treatment. There was significant heterogeneity. TCM might have a better survival and a higher complete response in patients with HRS. However, the quality of published studies was unsatisfactory.

Response-adapted radiation therapy for newly diagnosed primary diffuse large B-cell lymphoma of the CNS treated with methotrexate-based systemic therapy

BackgroundFor patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL), whole-brain radiation therapy (WBRT) to doses of ≥45 Gy are often given after a partial response (PR) to methotrexate-based induction chemotherapy. We conducted an exploratory analysis to determine whether lower-dose WBRT, given with a boost to sites of persistent disease, might be a reasonable alternative. Methods and materialsWe retrospectively reviewed the records of 22 patients with PCNSL who received WBRT, with or without a boost, after methotrexate-based induction chemotherapy. Outcomes were compared among patients according to response to chemotherapy using the Kaplan-Meier method. ResultsMedian follow-up was 52 months. All patients with a complete response (CR) (n = 5) received WBRT to 23.4 Gy. One CR patient died after an in-field relapse. Patients with partial response (PR) (n = 10) received a median whole-brain dose of 23.4 Gy with (n = 8) or without (n = 2) a boost; there were 2 relapses within the central nervous system (CNS). All PR patients were alive at the time of analysis. The overall survival (P = .127) and freedom from relapse within the CNS (P = .967) were not different for patients with CR versus PR. Baseline and follow-up neurocognitive evaluations were available for 4 PR patients, and there were no significant differences between pre- and post-treatment evaluations (P > .05 for language, memory, visual-spatial, attention, or motor functions). All patients who progressed or did not respond to chemotherapy and then received WBRT had died at a median time of 3.4 months. Patients who progressed or did not respond to chemotherapy had worse overall survival (P = .001) and freedom from CNS relapse (P = .005) compared with CR patients. ConclusionsAmong patients with a PR to induction chemotherapy, reduced-dose WBRT with a boost to residual PCNSL may be a viable treatment approach that merits further investigation.

Abstract 2785: Potency-matched dual cytokine antibody fusion proteins in combination with PD-L1 blockade

Abstract Among the different pharmacological approaches for cancer treatment, antibody-cytokine fusion proteins (also called “immunocytokines”) represent an emerging class of biopharmaceutical products, capable of boosting the immune system to attack tumor cells. These products promote the selective accumulation of pro-inflammatory molecules at the site of disease, mediated by the antibody fragment. These fusion proteins have been designed to reduce the systemic toxicity of traditional cytokines, currently approved for certain malignancies. Immunocytokine products based on interleukin-2 (IL2), interleukin-12 (IL12) or tumor necrosis factor (TNF) have been extensively studied in mouse model of cancer and in patients. When used as single agents, immunocytokines are often not able to cure mice and patients. However it as been shown by our group that the combination of IL2- and TNF- based products was capable to completely eradicate tumors in mouse models and to induce complete responses in patients. The development of combination products at the industrial level leads to a duplication of activities and costs. On the other hand, the opportunity to develop products with two payloads fused into a single molecular entity may facilitate development. This approach is limited by the fact that different cytokines often show different maximal tolerated doses (MTDs), and their relative potency need to be tuned. For example, TNF is administered at a dose, which is ten times lower compered to the one of IL2. We have recently described a novel class of immunocytokine products, termed “potency-matched dual cytokine antibody fusion proteins” consisting of a tumor-targeting antibody (for example F8, specific to the alternatively spliced EDA domain of fibronectin), simultaneously fused to both IL2 and TNF. To match biological activity of the two payloads a single-point mutation was inserted in the TNF sequence and the resulting product, named IL2-F8-TNFmut was able to selectively localize to lesions with an excellent tumor-to-organ ratios and it was found to completely eradicate soft-tissue sarcomas in immunocompetent mice, which did not respond to standard chemotherapy. We now report that complete responses were observed in a variety of mouse models of cancer and that the therapeutic efficacy of IL2-F8-TNFmut was further improved when used in combination with an anti-PD-L1 antibody. Potency-matched dual cytokine antibody fusion proteins may find clinical applications for various types of malignancies, used either as single agents or in combination with immune-checkpoint inhibitors. Citation Format: Roberto De Luca, Dario Neri. Potency-matched dual cytokine antibody fusion proteins in combination with PD-L1 blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2785.

Abstract 3811: Targeted Interleukin 2 and synergy with immune check-point inhibitors

Abstract Systemic high-dose Interleukin 2 (IL2) is able to elicit complete responses in patients suffering from metastatic melanoma. However, the majority of patients cannot receive the whole treatment dose due to severe toxicities. Other approved drugs for the treatment of metastatic melanoma include chemotherapeutics (e.g. Dacarbazine), a protein kinase B-raf inhibitor (Vemurafenib) and an immune check-point inhibitor (Ipilimumab, an anti CTLA-4 antibody). These drugs provide a clear benefit to patients, but cancer cures are still rare. Targeting IL2 to the site of disease represents a promising strategy to circumvent the toxicity and maximize the efficacy of this immunomodulatory payload. Various formats of targeted IL2 fusion proteins are currently in clinical development. Furthermore, recent successful approaches in the field of immunotherapy focus on the inhibition of check-point pathways, aiming to release the immunosuppressive brakes of the immune system. To explore the possibility of improving therapeutic efficacy of the single agents, a targeted version of IL2 (namely F8-IL2, where the F8 antibody recognizes the alternatively-spliced extra-domain A of fibronectin) was investigated in combination with an anti PD-1, anti PD-L1, or anti CTLA-4 antibody in an immunocompetent mouse model of CT26 colon carcinoma. In a first study, the combination of F8-IL2 and CTLA-4 blockade led to significant tumor growth retardation (curing 3/ 5 mice). Increasing the dose of F8-IL2 from 30 to 45 µg led to a 100 % cure rate with no signs of toxicity (body weight loss &amp;lt;5 %). Moreover, all cured mice acquired protective long-term immunity, which prevented tumor growth upon subsequent rechallenge with CT26 colon carcinoma cells. Furthermore, high dose F8-IL2 combined with the anti PD-1 antibody showed better therapeutic results than the respective monotherapies. In contrast, combination of F8-IL2 with the anti PD-L1 antibody did not improve the therapeutic outcome. Taken together, these data provide a strong rationale for the clinical use of targeted IL2 in combination with Ipilimumab. Citation Format: Cornelia Deborah Hutmacher-Berndt, Dario Neri. Targeted Interleukin 2 and synergy with immune check-point inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3811.

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution.

PurposeWe aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes.Materials and MethodsTotal 19 patients confirmed with MF between 1999–2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed.ResultsEleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT.ConclusionBoth IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

Clinical characteristics and treatment strategies for early-stage primary gastric diffuse large B-cell lymphoma

Objective: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is the most common non-Hodgkin lymphoma (NHL) of extranodal origin. Most patients with PG-DLBCL had localized disease (stage Ⅰ or Ⅱ) at presentation, and will achieve complete response (CR) after induction chemotherapy. However, there has been little consensus regarding whether optimal treatment is provided by chemotherapy alone or chemotherapy plus radiotherapy, nor the treatment outcome from the addition of rituximab in localized-stage PG-DLBCL. Methods: Patients with Stage ⅠE and ⅡE PG-DLBCL were retrospectively analyzed. Patients have not undergone surgery, have received at least 3 cycles of R-CHOP or CHOP-like chemotherapy as initial therapy, and achieved CR or partial response (PR) were enrolled. Results: A total of 91 patients were studied. The median age was 51 years, included 47 males and 44 females. Fifty-two patients were at Stage ⅠE and 39 at Stage ⅡE, 64 (70.3%) patients received R-CHOP-like regimens, and 27 (29.7%) received CHOP-like regimens, the median chemotherapy cycle was 6 (3-8). Among the 91 patients, 80 (87.9%) patients achieved CR from induction chemotherapy, 11(12.1%) was evaluated PR. Of CR patients, 48 patients (60%) underwent consolidating radiotherapy and 32 patients (40%) did not receive radiotherapy; all PR patients received salvage radiotherapy. CR patients with and without radiation therapy had 4-year progression-free survival (PFS) rates of 96.4% and 96.7%, respectively (χ(2) = 0.546, P=0.46); 7/11 (63.6%) PR patients achieved CR after radiotherapy, with a median follow-up of 41 months, they were all disease free. For patients treated with R-CHOP or CHOP-like regimens, the 4-year PFS was 93.2% and 89.7%, respectively (χ(2)=0.096, P=0.757). Conclusions: Consolidation radiotherapy failed to improve the outcome for early-stage PG-DLBCL, while for PR patients, salvage radiotherapy increased CR rate and improved survival. The addition of rituximab to CHOP did not improve the efficacy.

Treatment Intensification With Autologous Stem Cell Transplantation and Lenalidomide Maintenance Improves Survival Outcomes of Patients With Newly Diagnosed Multiple Myeloma in Complete Response

BackgroundHigh-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy. Patients and MethodsWe analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m). ResultsOverall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy. ConclusionEven in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy.

Diagnostic accuracy of MRI in assessing tumor regression and identifying complete response in patients with locally advanced rectal cancer after neoadjuvant treatment.

The diagnostic accuracy of Magnetic Resonance Imaging (MRI) in restaging locally advanced rectal cancers (LARC) after neoadjuvant chemo-radio therapy (NCRT) has been under recent scrutiny. There is limited data on the accuracy of MRI and its timing in assessing tumor regression grade (TRG) and in identifying patients with complete response (CR). NCRT seems to cause tissue inflammation and oedema which renders reading the scans difficult for radiologist. This study aims to assess the accuracy of MRI at different time intervals after NCRT in staging TRG and in identifying CR. Inter-observer agreement between 2 blinded radiologists will also be assessed. In this retrospective analysis, all patients diagnosed with LARC between January 2003 and 2014, who underwent long-course NCRT, who had at least one post-treatment MRI scan, and who underwent surgery with available pathology results are included. Histopathology staging is considered the reference standard. Accuracy of MRI in T staging and in TRG staging is assessed using weighted kappa. Accuracy, sensitivity, and specificity in identifying CR are calculated from a 2 × 2 contingency table. Inter-observer agreement between two-staging blinded radiologists is calculated using weighted kappa. These are calculated at 2 different time intervals after completion of NCRT. 114 patients were identified who had a first post-treatment MRI scan at an average of 6.2weeks after completion of NCRT. A subgroup of 68 patients had a second post-treatment MRI at an average of 10.4weeks. Pathology results were available for 103 patients. By the second post-treatment scan, an additional 25% of patients experienced downstaging; accuracy in T staging increased from 43% to 57.4%; accuracy in TRG staging rose from 28.2% to 38.1%; accuracy in identifying CR rose from 83.4% to 84.1%. Inter-observer agreement in T staging rose from 0.1 for first post-treatment MRI to 0.206 for second post-treatment MRI. This study advocates that restaging should occur at 10weeks rather than the standard 6weeks. This results in higher complete response rates and higher concordance with pathological specimens. Our results also showed that it is easier for radiologists to stage the MRI scans, resulting in higher inter-rater agreements.

Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy

PurposeTo clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Material and methodsFifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. ResultsMultiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az1), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az2), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az3), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az1 and Az2 were significantly higher than that of Az3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az1 and Az2 (P = 0.825). ConclusionQuantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC.

395 (PB-028) - Predictive Factors to Achieve Pathologic Complete Response in Patients with Locally Advanced Breast Cancer in Decision Making for more Conservative Management

395 (PB-028) - Predictive Factors to Achieve Pathologic Complete Response in Patients with Locally Advanced Breast Cancer in Decision Making for more Conservative Management

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

Purpose To assess the value of baseline and restaging fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

MR Imaging of Rectal Cancer: Radiomics Analysis to Assess Treatment Response after Neoadjuvant Therapy.

Purpose To investigate the value of T2-weighted-based radiomics compared with qualitative assessment at T2-weighted imaging and diffusion-weighted (DW) imaging for diagnosis of clinical complete response in patients with rectal cancer after neoadjuvant chemotherapy-radiation therapy (CRT). Materials and Methods This retrospective study included 114 patients with rectal cancer who underwent magnetic resonance (MR) imaging after CRT between March 2012 and February 2016. Median age among women (47 of 114, 41%) was 55.9 years (interquartile range, 45.4-66.7 years) and median age among men (67 of 114, 59%) was 55 years (interquartile range, 48-67 years). Surgical histopathologic analysis was the reference standard for pathologic complete response (pCR). For qualitative assessment, two radiologists reached a consensus. For radiomics, one radiologist segmented the volume of interest on high-spatial-resolution T2-weighted images. A random forest classifier was trained to separate the patients by their outcomes after balancing the number of patients in each response category by using the synthetic minority oversampling technique. Statistical analysis was performed by using the Wilcoxon rank-sum test, McNemar test, and Benjamini-Hochberg method. Results Twenty-one of 114 patients (18%) achieved pCR. The radiomic classifier demonstrated an area under the curve of 0.93 (95% confidence interval [CI]: 0.87, 0.96), sensitivity of 100% (95% CI: 0.84, 1), specificity of 91% (95% CI: 0.84, 0.96), positive predictive value of 72% (95% CI: 0.53, 0.87), and negative predictive value of 100% (95% CI: 0.96, 1). The diagnostic performance of radiomics was significantly higher than was qualitative assessment at T2-weighted imaging or DW imaging alone (P < .02). The specificity and positive predictive values were significantly higher in radiomics than were at combined T2-weighted and DW imaging (P < .0001). Conclusion T2-weighted-based radiomics showed better classification performance compared with qualitative assessment at T2-weighted and DW imaging for diagnosing pCR in patients with locally advanced rectal cancer after CRT. © RSNA, 2018 Online supplemental material is available for this article.

Can We Reliably Predict a Clinical Complete Response in Rectal Cancer? Current Trends and Future Strategies

Prediction of clinical complete response is pivotal in the management of patients with rectal cancer. The ability to determine tumor response to neoadjuvant therapy in rectal cancer might guide subsequent treatment modalities. We review the current literature on predictors of complete response after neoadjuvant for rectal cancer with an emphasis of clinical complete response rather than pathological complete response. Clinical and radiological findings have been used to predict response, as well as a myriad of biomarkers. There is limited evidence validating most of these strategies. The role of imaging in defining tumor response has been assessed retrospectively. The TRIGGER trial is a randomized trial that will evaluate stratified management of rectal cancer based on their tumor regression grade. The management of locally advanced rectal cancer is evolving. The ability to predict clinical complete response in patients that have undergone neoadjuvant chemoradiation will allow us to select potential patients that can benefit from a “watch and wait” strategy. Identifying patients that will have a complete response will result in decreased surgical overtreatment, favoring organ-sparing strategies. Treatment individualization will require further research. Emphasis should be made in validating prediction markers; these should be cost-effective and of minimally invasive retrieval. Surveillance protocols to assess for tumor regrowth are yet to be determined.

High dose interleukin-2 and response in 944 patients with metastatic renal cell cancer (RCC): Data from the PROCLAIM registry.

624 Background: High dose interleukin-2 (HD IL2) has traditionally been dosed every 8 hours for a maximum of 14 doses each cycle. We evaluated whether alternate dosing schedules and dose intensity affected achievement of complete response (CR) or partial response (PR) in the PROCLAIM registry. Methods: Patients with metastatic RCC were enrolled retrospectively and prospectively into the PROCLAIM registry to collect outcome data. Statistical methods for comparisons were done using Fisher’s and Chi Square tests. Results: From 2006-2017 the registry included 944 RCC patients; 257 (27%) women, 676 (72%) men. 844 (89%) were white. Histologic distribution: 624 (66%) clear cell, 93 (10%) medullary, 79 (8%) collecting duct, 78 (8%) chromophobe and 70 (7%) papillary. 207 (22%) had prior therapy with VEGF/mTOR. Best response was 51 (5.4%) CR and 169 (17.9%) PR; 263 (28%) progressive disease. 13 (1.4%) patients received q12 hour dosing while 830 (88%) received q8 hour dosing. 608 (64%) received 600 KIU/kg and 67 (7%) received 720 KIU/kg. Median # of doses in cycle 1 was 10 for CR and PR patients at 600 KIU/kg and 9 for those with stable or progressive disease. In the 720 KIU/kg group median #doses was 11 for CR, 8 for PR, and 7 for stable or progressive disease. In cycle 2 median doses received was 7.16 for patients with CR, 7.02 for PR and 6.76 for stable disease. Median dose intensity is similar at these two dose levels. Associations with achievement of CR/PR are summarized in the Table. Conclusions: There is no difference in response rate based on dosing schedule but the small number of subjects dosed q12 hours limits interpretation. Good performance patients possess the best opportunity for benefit from HD IL2. There is a trend for response with higher median # doses. Further studies of alternate dosing schedules are warranted. Clinical trial information: NCT01415167. [Table: see text]