Independent Radiological Evaluation of Objective Response, Early Tumor Shrinkage, and Depth of Response in Fire-3 (Aio Krk-0306) in the Final Ras Evaluable Population

In their article, Fucà et al highlight that early tumor shrinkage and depth of response predict the prognosis of patients with metastatic colorectal cancer (mCRC) microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) treated by immune checkpoint inhibitors (ICI). We are surprised that no cases of pseudoprogression (PSPD) were reported in their study. PSPDs were described under ICI in patients treated for MSI/dMMR mCRC. In a cohort of 123 patients treated with anti-PD1±antiCTL-4 for MSI/dMMR mCRC, we reported 12 patients with PSPD, representing 10% of the cohort. Of 12 patients with PSPD, 8 secondary achieved an objective response and were alive and free of progression at the data lock. Conversely, in Fucà’s article, no PSDP was observed and the patients with primary radiological progression (21.7%) had a poor overall survival. These differences between the two series could be probably explained by the following points. First, Fucà et al use RECIST 1.1 criteria for radiological evaluation. Second, the first imaging was done after 8–9 weeks of treatment in Fucà’s article, which may be late to detect PSPD. In conclusion, if the first evaluation is made during the first 3 months of treatment, using iRECIST criteria seems mandatory to avoid stopping treatment prematurely, especially in patients receiving anti-PD1 alone.

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Early Tumor Shrinkage and Depth of Response in the Second-Line Treatment for KRAS exon2 Wild-Type Metastatic Colorectal Cancer: An Exploratory Analysis of the Randomized Phase 2 Trial Comparing Panitumumab and Bevacizumab in Combination with FOLFIRI (WJOG6210G)

Targeted Oncology ◽

10.1007/s11523-020-00750-w ◽

2020 ◽

Vol 15 (5) ◽

pp. 623-633

Author(s):

Naoki Izawa ◽

Kohei Shitara ◽

Kimio Yonesaka ◽

Takeharu Yamanaka ◽

Takayuki Yoshino ◽

...

Keyword(s):

Tumor Shrinkage ◽

Line Treatment ◽

Second Line ◽

Phase 2 ◽

Wild Type ◽

Phase 2 Trial ◽

Depth Of Response ◽

Early Tumor Shrinkage ◽

Early Tumor ◽

Randomized Phase 2

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Impact of Size and Location of Metastases on Early Tumor Shrinkage and Depth of Response in Patients With Metastatic Colorectal Cancer: Subgroup Findings of the Randomized, Open-Label Phase 3 Trial FIRE-3/AIO KRK-0306

Clinical Colorectal Cancer ◽

10.1016/j.clcc.2020.06.005 ◽

2020 ◽

Vol 19 (4) ◽

pp. 291-300.e5

Author(s):

Matthias F. Froelich ◽

Elina L. Petersen ◽

Volker Heinemann ◽

Dominik Nörenberg ◽

Nina Hesse ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Tumor Shrinkage ◽

Open Label ◽

Phase 3 ◽

Depth Of Response ◽

Early Tumor Shrinkage ◽

Open Label Phase ◽

Early Tumor

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Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study

Cancers ◽

10.3390/cancers11070939 ◽

2019 ◽

Vol 11 (7) ◽

pp. 939 ◽

Cited By ~ 1

Author(s):

Caterina Vivaldi ◽

Lorenzo Fornaro ◽

Carla Cappelli ◽

Irene Pecora ◽

Silvia Catanese ◽

...

Keyword(s):

Pancreatic Cancer ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Tumor Shrinkage ◽

First Line ◽

Free Survival ◽

Depth Of Response ◽

Early Tumor Shrinkage ◽

Early Tumor

Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions’ longest diameters (SLD) after 6–8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group; p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p < 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was −27.5% (−29.4% with FOLFOXIRI and −21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p < 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.

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Early Tumor Shrinkage as a Predictive Factor for Outcomes in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Analysis

Cancers ◽

10.3390/cancers12030754 ◽

2020 ◽

Vol 12 (3) ◽

pp. 754 ◽

Cited By ~ 3

Author(s):

Aya Takahashi ◽

Michihisa Moriguchi ◽

Yuya Seko ◽

Toshihide Shima ◽

Yasuhide Mitsumoto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Characteristic Curve ◽

Objective Response ◽

Evaluation Criteria ◽

Treatment Decision ◽

Progression Free Survival ◽

Tumor Shrinkage ◽

Discrimination Ability ◽

Early Tumor Shrinkage ◽

Early Tumor

We investigated the association between early tumor shrinkage (ETS) and treatment outcome in patients with hepatocellular carcinoma treated with lenvatinib (LEN). A retrospective analysis was performed in 104 patients. ETS was defined as tumor shrinkage at the first evaluation in the sum of target lesions’ longest diameters from baseline according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 5.0 months. The receiver operating characteristic curve analysis in differentiating long-term responders (PFS ≥ 5.0 months) from short-term responders (PFS < 5.0 months) revealed an ETS cut-off value of 10%. ETS ≥ 10% was significantly correlated with better PFS and OS compared with ETS < 10%. Additionally, ETS ≥ 10% showed a better discrimination ability on prognosis compared with modified RECIST-based objective response at the first evaluation. Multivariate analysis confirmed ETS ≥ 10% as an independent predictor of better OS, as well as a Child–Pugh score of 5 and macrovascular invasion. In conclusion, ETS ≥ 10% was strongly associated with outcome in patients treated with LEN. This biomarker could allow earlier assessment of the treatment response and guide treatment decision-making for HCC.

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Right-sided colorectal cancer (RC): Response to first-line chemotherapy in FIRE-3 (AIO KRK-0306) with focus on early tumor shrinkage (ETS) and depth of response (DpR).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3586 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3586-3586 ◽

Cited By ~ 3

Author(s):

Julian Walter Holch ◽

Sebastian Stintzing ◽

Swantje Held ◽

Ludwig Fischer von Weikersthal ◽

Thomas Decker ◽

...

Keyword(s):

Colorectal Cancer ◽

Rank Test ◽

Tumor Shrinkage ◽

First Line ◽

Depth Of Response ◽

Kaplan Meier ◽

Hazard Ratios ◽

Radiological Data ◽

Early Tumor Shrinkage ◽

Early Tumor

3586 Background: Recent evidence suggests that benefit from anti-EGFR treatment is restricted to RAS wild-type left-sided colorectal cancer (LC) (Holch JW et al. Eur J Cancer 2017). However, these results are preliminary. We therefore investigated patients with RC enrolled in the FIRE-3 trial, which evaluated the efficacy of first-line FOLFIRI plus either cetuximab (cet) or bevacizumab (bev) in RAS wildtype mCRC. New metrics of tumor dynamics were used to characterize the patients. Methods: The splenic flexure was used to differentiate LC from RC. Survival analysis was done using Kaplan-Meier estimation and differences were expressed using Log-Rank test, hazard ratios (HR) and corresponding 95% confidence intervals. Central independent radiological data was used to calculate early tumor shrinkage ≥20% (ETS) and depth of response (DpR). Results: In total, 330 patients were assessable for central radiological evaluation. In patients with LC (n = 257), treatment with FOLFIRI + cet led to longer overall survival (OS) compared to FOLFIRI + bev (HR = 0.68, p = 0.016). In patients with RC (n = 68), OS was comparable between treatment arms (HR = 1.11, p = 0.715). In patients with RC and ETS < 20%, OS was inferior in patients treated with FOLFIRI + cet. In patients who reached ETS ≥20%, a comparable OS was evident between treatment arms (for further details of efficacy in patients with RC see table). Conclusions: Patients with RC do not represent a uniform population. ETS ≥20% defines a subgroup of patients where comparable treatment efficacy was observed with regard to OS, ORR and DpR by addition of cetuximab vs. bevacizumab to FOLFIRI. [Table: see text]

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