Letter: Tumor Growth Rate as a New Predictor of Progression-Free Survival After Chordoma Surgery

Abstract INTRODUCTION The pivotal EF-14 trial showed that Tumor Treating Fields (TTFields) extend Progression Free Survival (PFS) in newly Diagnosed Glioblastoma (ndGBM) patients. This leads to the hypothesis that TTFields therapy leads to local control of tumors, yielding a significant decrease in tumor growth rates. Here we present an analysis testing this hypothesis in biopsy-only patients who participated in the EF-14 trial. METHODS Biopsy patients of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=37/60, control: N=12/29). Volumes of enhancing tumor were segmented on T1c MRIs at baseline and at progression. Tumor growth rate was calculated as: growth_rate=(ln(v0)-ln(v1))/dt. (v0- tumor volume at baseline), v1- Tumor volume at progression, dt- days to progression), which models tumor volume as increasing exponentially over time. Median growth rates in the treatment and control arms were compared. RESULTS The median growth rate was lower in the treatment arm than in the control. (control: 0.14±0.12 mL/month, TTFields -0.011±0.11 mL/month, p< 0.008 Wilcoxon rank-sum) DISCUSSION AND CONCLUSIONS This study shows that tumor growth rates are slower in patients treated with TTFileds+Temozolomide (TMZ) than in patients treated with TMZ alone. This analysis was restricted to biopsy-only patients since the definition of tumor volume is ambiguous in patients that underwent resection since a large portion of the tumor has been removed. The negative median growth rate for patients in the treatment arm may indicate that a significant number of TTFields-treated patients a decrease in tumor volume was observed, suggesting that TTFields enhances local tumor control. References: [1] Stupp, Roger, et al. Jama 318.23 (2017): 2306–2316.[[2 Stensjøen, Anne Line, et al. Neuro-oncology 17.10 (2015): 1402–1411.

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Tumor growth rate in pancreatic neuroendocrine tumor patients undergoing PRRT with 177Lu-DOTATATE

Endocrine Connections ◽

10.1530/ec-21-0027 ◽

2021 ◽

Vol 10 (4) ◽

pp. 422-431

Author(s):

Olof Joakim Pettersson ◽

Katarzyna Fröss-Baron ◽

Joakim Crona ◽

Anders Sundin

Keyword(s):

Growth Rate ◽

Survival Analysis ◽

Tumor Growth ◽

Cox Regression ◽

Peptide Receptor Radionuclide Therapy ◽

Progression Free Survival ◽

Pancreatic Neuroendocrine Tumor ◽

Tumor Growth Rate ◽

Ki 67 ◽

Contrast Enhanced Ct

Background Monitoring of pancreatic neuroendocrine tumors (PanNET) undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE depends on changes in tumor size, which often occur late. Tumor growth rate (TGR) allows for quantitative assessment of the tumor kinetics expressed as %/month. We explored how TGR changes before and during/after PRRT and evaluated TGR as a biomarker for progression-free survival (PFS). Methods In PanNET patients undergoing PRRT with 177Lu-DOTATATE from 2006 to 2018, contrast-enhanced CT or MRI was performed before and during the therapy. Patients with at least one hypervascular liver metastasis were included. TGR was calculated for the period preceding treatment and for two intervals during/after PRRT. Cox regression was used for the survival analysis. Results Sixty-seven patients (43 men, 24 women), median age 60 years (range 29–77), median Ki-67 10% (range 1–30) were included. TGR before baseline (n = 57) (TGR0) was mean (s.d.) 6.0%/month (s.d. = 8.7). TGR at 4.5 months (n = 56) (TGR4) from baseline was −3.4 (s.d. = 4.2) %/month. TGR at 9.9 months (n = 57) (TGR10) from baseline was −3.0 (s.d. = 2.9) %/month. TGR4 and TGR10 were lower than TGR0 (TGR4 vs TGR0, P < 0.001 and TGR10 vs TGR0, P < 0.001). In the survival analysis, patients with TGR10 ≥ 0.5%/month (vs <0.5%/month) had shorter PFS (median = 16.0 months vs 31.5 months, hazard ratio 2.82; 95% CI 1.05–7.57, P = 0.040). Discussion TGR in PanNET patients decreases considerably during PRRT with 177Lu-DOTATATE. TGR may be useful as a biomarker to identify patients with the shortest PFS.

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Tumor growth rate as an early indicator of the efficacy of anti-PD-1 immunotherapy in advanced melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e21050 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e21050-e21050 ◽

Cited By ~ 1

Author(s):

Bixia Tang ◽

Zhihong Chi ◽

Xinan Sheng ◽

Lu Si ◽

Chuanliang Cui ◽

...

Keyword(s):

Growth Rate ◽

Clinical Trials ◽

Tumor Growth ◽

Objective Response ◽

Antibody Therapy ◽

Progression Free Survival ◽

Tumor Growth Rate ◽

Imaging Data ◽

Pretreatment Period ◽

Tumor Measurements

e21050 Background: As immunotherapeutics take longer time to show clinical efficacy compared with chemotherapy and targeted therapy, it is critical to select patients with low tumor growth rate (TGR) prior immunotherapy as to get sufficient time for immunotherapeutics to play functions. However, which threshold of TGR before immunotherapy may be associated with good outcome remains unknown. Methods: Medical records from patients with advanced refractory melanoma prospectively treated in clinical trials (NCT02836795 and NCT03013101) of anti-PD-1 antibody toripalimab were analyzed. TGR was computed during the pretreatment period (reference) and the treatment period (treatment). Associations between TGR and objective response at the first evaluation, progression free survival (PFS), overall survival (OS) were computed. Results: We analyzed a total of 142 patients enrolled in these two clinical trials. Excluded for no measurable lesions in pretreatment period or incomplete imaging data through the pretreatment/treatment periods, a total of 90 patients could be explored for the relationship of TGR and the efficacy of anti-PD-1 antibody. TGR and hyperprogression were defined as Champiat S. used to make. The distribution of TGR is as follows: median 63.7 (range: -51~720). A total of 15 (16.7%), 41 (45.6%), 34 (37.8%) and 0 patients exhibited PR, SD, PD, CR, respectively. An association between lower TGR (TGR ≤55) and objective response was observed (P≤0.001). Among evaluable patients at week 8, 83.9% (13+34/56) and 26.5% (2+7/34) showed PR/SD from baseline tumor measurements for the group of TGR≤55 and TGR > 55, respectively. Median PFS was 5.5 0.9m in the group of TGR≤55 compared 1.8 0.4m in the group of TGR > 55 (P≤0.001). Median OS was not reached in the group of TGR≤55 group and was 15.9 1.8m in the group of TGR > 55 (p = 0·02). Two patients were confirmed pseudoprogression in the follow-up. The TGR of these two patients was lower than 55. Five patients experienced hyperprogression. The TGR of each patient was 9, 12, 54, 56, 78, respectively. Conclusions: Melanoma patients with TGR≤55 prior anti-PD-1 antibody therapy are more likely to benefit from this regimen. However, it could not predict patients who may develop hyperprogression after anti-PD-1 antibody therapy. Clinical trial information: NCT02836795 and NCT03013101.

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An FDA analysis of the association of tumor growth rate and overall and progression-free survival in metastatic non-small cell lung cancer (NSCLC) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9541 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9541-9541

Author(s):

Yutao Gong ◽

Jeremy Mason ◽

Yuan-Li Shen ◽

Elaine Chang ◽

Dickran Kazandjian ◽

...

Keyword(s):

Lung Cancer ◽

Growth Rate ◽

Clinical Trials ◽

Progression Free Survival ◽

Small Cell ◽

Tumor Growth Rate ◽

Small Cell Lung ◽

Free Survival ◽

Tumor Measurements ◽

Line Of Therapy

9541 Background: Previous studies have suggested that tumor growth rate (g), estimated using prostate-specific antigen values, is associated with overall survival (OS) in prostate cancer (Wilkerson, 2016). We performed a retrospective pooled analysis in non-small cell lung cancer (NSCLC) to investigate the extent to which g values estimated using radiological tumor measurements in clinical trials are associated with survival. Methods: We identified 24 randomized clinical trials submitted to FDA between 2013 and 2019 investigating either immune checkpoint inhibitor (ICI) or targeted therapy (TT) in pts with metastatic NSCLC. Of 9934 patients (pts) enrolled, 5532 pts (2401, 1189, and 1942 pts treated with ICI, TT, and chemotherapy respectively) had sufficient data to derive a valid g. The g was evaluated by both type and line of therapy. Pts were then grouped according to quartiles of g, with Q1 being the lowest. We calculated OS and progression-free survival (PFS) for each group via the Kaplan-Meier method, and used the Cox model for group comparison. Results: Median g was 9.7E-4, 1.4E-3, and 2.2E-3/day, and median OS was 34.2, 21.3, and 15.3 months (mo), in pts treated with TT, ICI, and chemotherapy, respectively, regardless of lines of therapy. When treated with the same type of therapy, pts receiving 2nd line therapy had a higher median g than those receiving 1st line. The median survival and log-rank hazard ratios for pts treated with 1st line ICI monotherapy are shown in the Table. Conclusions: TT is associated with the lowest median g, followed by ICI, and then chemotherapy, perhaps due to patient selection, better inherent biology/natural history, or favorable results of TT on selected tumors. Regardless, we found that g is inversely associated with survival, across treatment types. This relationship is also observed in pts treated with the same type and line of therapy (for example, 1st line ICI), where Q1 has the longest survival, followed by Q2, Q3, and then Q4. In summary, our exploratory analysis suggests that g derived from radiological tumor measurements in NSCLC may relate to survival. Prospective studies are needed to evaluate if g might be an earlier endpoint compared to classical response criteria. [Table: see text]

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Tumor Growth Rate as a Prognostic Factor for Metastatic or Recurrent Adenoid Cystic Carcinoma of the Head and Neck Patients Treated with Carboplatin Plus Paclitaxel

10.21203/rs.3.rs-26488/v1 ◽

2020 ◽

Author(s):

Naoki Fukuda ◽

Yu Fujiwara ◽

Xiaofei Wang ◽

Akihiro Ohmoto ◽

Tetsuya Urasaki ◽

...

Keyword(s):

Growth Rate ◽

Prognostic Factors ◽

Tumor Growth ◽

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Objective Response ◽

Progression Free Survival ◽

Tumor Growth Rate ◽

Adenoid Cystic ◽

Exploratory Investigation

Abstract Background: Large prospective studies of chemotherapy for metastatic or recurrent adenoid cystic carcinoma (ACC) of the head and neck are lacking due to the rarity of ACC. The aim of this study is to evaluate the efficacy of carboplatin plus paclitaxel toward ACC and perform an exploratory investigation of the prognostic factors to investigate the optimal strategy for metastatic or recurrent ACC.Methods: We retrospectively analyzed recurrent or metastatic ACC patients treated with carboplatin plus paclitaxel between April 2007 and September 2019 in our hospital. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated, and an exploratory analysis of the prognostic factors including tumor growth rate (TGR) was conducted.Results: A total of 26 ACC patients were enrolled. ORR and DCR were 11.5% and 76.9%; the median PFS and OS were 8.1 and 22.3 months, respectively. From the results of the multivariate analysis, higher (≥ 6%/month) TGR was associated with worse PFS (hazard ratio [HR] 7.00, 95%CI 1.34–36.53, p = 0.02) and OS (HR 29.33, 95%CI 3.38–254.80, p < 0.01). The median PFS (10.6 vs. 6.6 months, log-rank p < 0.05) and OS (48.5 vs. 16.9 months, log-rank p < 0.01) were significantly shorter in patients with higher TGR.Conclusions: Carboplatin plus paclitaxel showed modest efficacy for recurrent or metastatic ACC patients. Watchful waiting may be optimal for ACC patients with lower TGR. Systemic chemotherapy should be considered when TGR increases during active surveillance.

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Tumor growth rate analysis of progression-free survival (PFS) and overall survival (OS) for thyroid cancer patients receiving placebo or sorafenib in the phase 3 DECISION trial

Annals of Oncology ◽

10.1093/annonc/mdw376.10 ◽

2016 ◽

Vol 27 ◽

pp. vi331 ◽

Cited By ~ 1

Author(s):

C. Kappeler ◽

G. Meinhardt ◽

R. Elisei ◽

M. Brose ◽

M. Schlumberger

Keyword(s):

Growth Rate ◽

Overall Survival ◽

Thyroid Cancer ◽

Cancer Patients ◽

Progression Free Survival ◽

Tumor Growth Rate ◽

Phase 3 ◽

Free Survival ◽

Rate Analysis ◽

Decision Trial

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Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults

Neuro-Oncology ◽

10.1093/neuonc/noaa022 ◽

2020 ◽

Vol 22 (7) ◽

pp. 993-1005 ◽

Cited By ~ 1

Author(s):

Alexandre Roux ◽

Arnault Tauziede-Espariat ◽

Marc Zanello ◽

Sophie Peeters ◽

Gilles Zah-Bi ◽

...

Keyword(s):

Growth Rate ◽

Tumor Growth ◽

Growth Rates ◽

Progression Free Survival ◽

World Health ◽

Tumor Growth Rate ◽

Who Grade ◽

Spontaneous Tumor ◽

Grade Ii ◽

Grade Iii

Abstract Background We quantified the spontaneous imaging growth rate of oligodendrogliomas. We assessed whether (i) it discriminates between World Health Organization (WHO) grade II and grade III oligodendrogliomas, and (ii) grade III oligodendrogliomas with neo-angiogenesis are associated with more fast growth rates (≥8 mm/y). Methods This work employed a retrospective bicentric cohort study (2010–2016) of adult patients harboring a newly diagnosed supratentorial oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (WHO 2016 classification), with a minimum of 2 available MRIs before any treatment (minimum 6-week interval) to measure the spontaneous tumor growth rate. Results We included 108 patients (age 44.7 ± 14.1 y, 60 males). The tumor growth rate was higher in grade III oligodendrogliomas with neo-angiogenesis (n = 37, median 10.4 mm/y, mean 10.0 ± 6.9) than in grade III oligodendrogliomas with increased mitosis count only (cutoff ≥6 mitoses, n = 18, median 3.9 mm/y, mean 4.5 ± 3.2; P = 0.004), and higher than in grade II oligodendrogliomas (n = 53, median 2.3 mm/y, mean 2.8 ± 2.2; P < 0.001). There was increased prevalence of fast tumor growth rates in grade III oligodendrogliomas with neo-angiogenesis (54.1%) compared with grade III oligodendrogliomas with increased mitosis count only (11.1%; P < 0.001), and in grade II oligodendrogliomas (0.0%; P < 0.001). The tumor growth rate trends did not differ between centers (P = 0.121). Neo-angiogenesis (P < 0.001) and mitosis count at ≥9 (P = 0.013) were independently associated with tumor growth rates ≥8 mm/year. A tumor growth rate ≥8 mm/year was the only predictor independently associated with shorter progression-free survival (P = 0.041). Conclusions The spontaneous tumor growth rate recapitulates oligodendroglioma aggressiveness, permits identification of grade III oligodendrogliomas preoperatively when ≥8 mm/year, and questions the grading by mitosis count.

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