Pretreatment Tumor Growth Research Articles

Pretreatment Tumor Growth Rate and Radiological Response as Predictive Markers of Pathological Response and Survival in Patients with Resectable Lung Cancer Treated by Neoadjuvant Treatment.

Predictive biomarkers associated with pathological response, progression precluding surgery, and/or recurrence after surgery are needed for patients with resectable non-small cell lung carcinoma (NSCLC) treated by neoadjuvant treatment. We evaluated the clinical impact of the pretreatment tumor growth rate (TGR0) and radiological response for patients with resectable NSCLC treated with neoadjuvant therapies. Consecutive patients with resectable stage IB (≥4 cm) to IIIA NSCLC treated by neoadjuvant platinum-doublet chemotherapy with or without nivolumab at our tertiary center were retrospectively analyzed. TGR0 and RECIST objective responses were determined. Multivariable analyses identified independent predictors of event-free survival (EFS), overall survival (OS), and major pathological response (MPR). Between November 2017 and December 2022, 32 patients (mean [SD] age, 63.8 [8.0] years) were included. At a median follow-up of 54.8 months (95% CI, 42.3-60.4 months), eleven patients (34%) experienced progression or recurrence, and twelve deaths (38%) were recorded. The TGR0 cutoff of 30%/month remained the only independent factor associated with EFS (HR = 0.04; 95% CI, 0.01-0.3; p = 0.003) and OS (HR = 0.2; 95% CI, 0.03-0.7; p = 0.01). The TGR0 cut-off had a mean time-dependent AUC of 0.83 (95% CI, 0.64-0.95) and 0.80 (95% CI, 0.62-0.97) for predicting EFS and OS, respectively. Fifteen of 26 resection cases (58%) showed MPR including nine with pathological complete responses (35%). Only the objective response of the primary tumor was associated with MPR (OR = 27.5; 95% CI, 2.6-289.1; p = 0.006). Assessment of TGR0 can identify patients who should benefit from neoadjuvant treatment. A tumor objective response might be a predictor of MPR after neoadjuvant treatment, which will help to adapt surgical management.

Mathematical prediction with pretreatment growth rate of metastatic cancer on outcomes: implications for the characterization of oligometastatic disease.

Oligometastatic disease (OMD) represents an indolent cancer status characterized by slow tumor growth and limited metastatic potential. The use of local therapy in the management of the condition continues to rise. This study aimed to investigate the advantage of pretreatment tumor growth rate in addition to baseline disease burden in characterizing OMDs, generally defined by the presence of ≤ 5 metastatic lesions. The study included patients with metastatic melanoma treated with pembrolizumab. Gross tumor volume of all metastases was contoured on imaging before (TP-1) and at the initiation of pembrolizumab (TP0). Pretreatment tumor growth rate was calculated by an exponential ordinary differential equation model using the sum of tumor volumes at TP-1 and TP0 and the time interval between TP-1. and TP0. Patients were divided into interquartile groups based on pretreatment growth rate. Overall survival, progression-free survival, and subsequent progression-free survival were the study outcomes. At baseline, median cumulative volume and number of metastases were 28.4 cc (range, 0.4-1194.8 cc) and 7 (range, 1-73), respectively. The median interval between TP-1 and TP0 was -90 days and pretreatment tumor growth rate (×10-2 days-1) was median 4.71 (range -0.62 to 44.1). The slow-paced group (pretreatment tumor growth rate ≤ 7.6 ×10-2 days-1, the upper quartile) had a significantly higher overall survival rate, progression-free survival, and subsequent progression-free survival compared to those of the fast-paced group (pretreatment tumor growth rate > 7.6 ×10-2 days-1). Notably, these differences were prominent in the subgroup with >5 metastases. Pretreatment tumor growth rate is a novel prognostic metric associated with overall survival, progression-free survival, and subsequent progression-free survival among metastatic melanoma patients, especially patients with >5 metastases. Future prospective studies should validate the advantage of disease growth rate plus disease burden in better defining OMDs.

Pre-treatment Tumor Size and Tumor Growth Rate as Prognostic Predictors for Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Nivolumab.

The prognosis of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is poor, although immune checkpoint inhibitors (ICIs), such as nivolumab, have been shown to prolong survival. We investigated the factors that predict the efficacy of nivolumab when selecting an appropriate treatment strategy for patients with R/M SCCHN. Forty-four Japanese patients with R/M SCCHN treated with nivolumab between May 2017 and October 2021 were analyzed. The primary endpoint of the study was overall survival (OS). We defined pre-treatment tumor size (PTS) as the sum of the size of all measurable lesions, and tumor growth rate (TGR) as the total growth rate of the largest tumor diameter on CT scans taken to determine treatment response, divided by the interval between CT scans. Receiver operating characteristic (ROC) curves were used to identify the cutoff points of PTS and TGR for OS. Cox proportional hazards regression analysis was performed to examine the relationships between various factors, including patient characteristics, PTS, and TGR, as well as treatment outcomes. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥1, progressive disease (PD) as best overall response (BOR), and TGR >0.60%/day were independent risk factors for poor OS in patients with R/M-SCCHN. Higher TGR, poor PS, and PD as BOR may be prognostic factors in patients with R/M SCCHN.

VERDICT MRI for radiation treatment response assessment in neuroendocrine tumors.

Noninvasive methods to study changes in tumor microstructure enable early assessment of treatment response and thus facilitate personalized treatment. The aim of this study was to evaluate the diffusion MRI model, Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT), for early response assessment to external radiation treatment and to compare the results with those of more studied sets of parameters derived from diffusion-weighted MRI data. Mice xenografted with human small intestine tumors were treated with external radiation treatment, and diffusion MRI experiments were performed on the day before and up to 2 weeks after treatment. The diffusion models VERDICT, ADC, IVIM, and DKI were fitted to MRI data, and the treatment response of each tumor was calculated based on pretreatment tumor growth and post-treatment tumor volume regression. Linear regression and correlation analysis were used to evaluate each model and their respective parameters for explaining the treatment response. VERDICT analysis showed significant changes from day -1 to day 3 for the intracellular and extracellular volume fraction, as well as the cell radius index (p<0.05; Wilcoxon signed-rank test). The strongest correlation between the diffusion model parameters and the tumor treatment response was seen for the ADC, kurtosis-corrected diffusion coefficient, and intracellular volume fraction on day 3 (τ =0.47, 0.52, and -0.49, respectively, p<0.05; Kendall rank correlation coefficient). Of all the tested models, VERDICT held the strongest explanatory value for the tumor treatment response on day 3 (R2 =0.75, p<0.01; linear regression). In conclusion, VERDICT has potential for early assessment of external radiation treatment and may provide further insights into the underlying biological effects of radiation on tumor tissue. In addition, the results suggest that the time window for assessment of treatment response using dMRI may be narrow.

Pre-Treatment Tumor Growth Rate Predicts Clinical Outcomes of Patients With Advanced Non-Small Cell Lung Cancer Undergoing Anti-PD-1/PD-L1 Therapy.

Tumor growth rate (TGR; percent size change per month [%/m]) is postulated as an early radio-graphic predictor of response to anti-cancer treatment to overcome limitations of RECIST. We aimed to evaluate the predictive value of pre-treatment TGR (TGR0) for outcomes of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1/PD-L1 monotherapy. We retrospectively screened all aNSCLC patients who received PD-1 axis inhibitors in Sun Yat-Sen University Cancer Center between August 2016 and June 2018. TGR0 was calculated as the percentage change in tumor size per month (%/m) derived from two computed tomography (CT) scans during a “wash-out” period before the initiation of PD-1 axis inhibition. Final follow-up date was August 28, 2019. The X-tile program was used to identify the cut-off value of TGR0 based on maximum progression-free survival (PFS) stratification. Patients were divided into two groups per the selected TGR0 cut-off. The primary outcome was the difference of PFS between the two groups. The Kaplan-Meier methods and Cox regression models were performed for survival analysis. A total of 80 eligible patients were included (54 [67.5%] male; median [range] age, 55 [30-74] years). Median (range) TGR0 was 21.1 (-33.7-246.0)%/m. The optimal cut-off value of TGR0 was 25.3%/m. Patients with high TGR0 had shorter median PFS (1.8 months; 95% CI, 1.6 - 2.1 months) than those with low TGR0 (2.7 months; 95% CI, 0.5 - 4.9 months) (P = 0.005). Multivariate Cox regression analysis revealed that higher TGR0 independently predicted inferior PFS (hazard ratio [HR] 1.97; 95% CI, 1.08-3.60; P = 0.026). Higher TGR0 was also significantly associated with less durable clinical benefit rate (34.8% vs. 8.8%, P = 0.007). High pre-treatment TGR was a reliable predictor of inferior PFS and clinical benefit in aNSCLC patients undergoing anti-PD-1/PD-L1 monotherapy. The findings highlight the role of TGR0 as an early biomarker to predict benefit from immunotherapy and could allow tailoring patient’s follow-up.

Validating impact of pretreatment tumor growth rate on outcome of early-stage lung cancer treated with stereotactic body radiation therapy.

BackgroundTo assess correlation of pretreatment specific growth rate (SGR) value of 0.43 × 10‐2 with overall and failure‐free survival of patients with early‐stage non‐small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT).MethodsA retrospective chart review of 160 patients with pathologically confirmed stage I NSCLC treated with SBRT between June 2010 and December 2012 in a large, tertiary cancer institute was undertaken. Both diagnostic and archived planning CT were uploaded to the treatment planning system to determine tumor volume at diagnosis (GTV1) and planning time (GTV2). The time (t) between both CTs was recorded. SGR was calculated using GTV1, GTV2, and t. The median SGR (0.43 × 10‐2) from our previous data was used to group patients into low and high SGR cohorts. Log‐rank test was used to compare overall (OS) and failure‐free survivals (FFS) of SGR groups.ResultsThe median time interval between diagnostic and planning CT scans was 87 days. The median OS was 38 and 66 months for high and low SGR cohorts, respectively (P = 0.03). The median FFS was 27 and 55 months for high and low SGR cohorts, respectively (P = 0.005). High SGR (P < 0.05), male gender (P = <0.01), and GTV2 (P = <0.05) were associated with poorer FFS.ConclusionsHigh SGR was associated with poorer outcome in patients with early‐stage NSCLC treated with SBRT. SGR can be used in conjunction with other well‐known predictive factors to formulate a practical predictive model to identify subgroups of the patient at higher risk of recurrence after SBRT.

Temozolomide Alone or Combined with Capecitabine for the Treatment of Metastatic Neuroendocrine Neoplasia: A “Real-World” Data Analysis

Background: Neuroendocrine neoplasias (NENs) are a rare group of tumors with different prognosis and response to therapy. Their heterogeneity is dependent on the site of origin, morphology, and Ki67. Temozolomide (TEM) appears to be active in metastatic NENs (mNENs) but there is limited evidence about its efficacy in gastrointestinal NENs. We analyzed “real-world” data on the use of TEM alone or in association with capecitabine (CAPTEM) in patients with mNENs. Patients and Methods: One hundred consecutive patients with advanced NENs treated with TEM or CAPTEM between 2009 and 2019 were included. A pretreatment tumor growth rate (TGR₀) was calculated. Overall survival (OS), progression-free survival (PFS), tolerance, objective response rate (ORR), and disease control rate (DCR) were analyzed. A propensity score analysis and inverse probability of treatment weights for Cox regression models were used. Results: TEM-based therapy was administered to 95 patients (26.3% CAPTEM and 83.7% TEM) with a median age of 59 years (range 26–85) years. ECOG performance status was 0–2. Carcinoid syndrome was reported in 12 (12.6%) patients. Twenty (21.1%) patients with grade (G) 3 neuroendocrine carcinoma (NEC) and 9 (9.4%) with G3 neuroendocrine tumors (NETs) were included in the analysis. Median PFS of the entire group was 10.4 months (95% confidence interval [CI]: 6.0–11.5). In multivariate analysis, a higher risk of progression was observed for NEC G3 patients (hazard ratio [HR] 2.70, 95% CI: 1.25–5.84) and for a TGR ≥19.55 (HR: 2.53, 95% CI: 1.45–4.40). Median OS was 23.4 months (95% CI: 17.0–29.0) and was similar in both treatment groups (23.9 vs. 20.5 months for TEM and CAPTEM, respectively, p = 0.585). In multivariate analysis, TGR ≥19.55 was associated with a higher risk of death (HR: 2.18, 95% CI: 1.16–4.11) than TGR <19.55, as was NEC G3 (HR: 2.42, 95% CI: 1.04–5.59) with respect to NETs. No differences in terms of mPFS or mOS were seen in relation to the primary site of disease. In the 86 patients evaluable for response, ORR was 44.1% and the DCR was 70.9%. Mild adverse events (grade I–II) included anemia, neutropenia, and headache. Rare cases of G 3 neutropenia and thrombocytopenia were recorded. Conclusions: TEM-based regimens are associated with a high DCR and a relatively tolerable toxicity profile in NENs of pancreatic, intestinal, and lung origin. Further investigation of these specific NETs is warranted in prospective clinical trials.

Therapeutically-induced stable disease in oncology early clinical trials.

RationaleThe RECIST guideline defines four categories of response to treatment for cancer patients according to post-baseline changes in tumor burden, hence ignoring disease history. However, if left untreated, tumors grow exponentially, implying that pretreatment changes in tumor size are key to thoroughly assess efficacy. We present a model-based approach to estimate the rates of changes in tumor mass, before and after treatment onset.MethodsSixty-eight patients were eligible for the analysis of tumor size data from a Phase 1 study evaluating the effect of emactuzumab. In addition to tumor size measured at baseline and every six weeks during treatment, a pre-baseline measurement was gathered for each patient. A longitudinal regression model was used to estimate the rates of tumor size change before and after treatment onset.ResultsThe median pre-treatment tumor growth exponential rate was equal to 0.022 month-1, corresponding to a tumor size doubling time of 4 months, and the on-treatment median tumor shrinkage exponential rate was equal to 0.001 month-1. Among sixteen patients categorized as stable disease per RECIST, only five had similar slopes before and after treatment while nine actually improved. One patient in particular had a therapeutically induced stabilization of the disease.ConclusionOur analysis emphasizes the importance of collecting pre-baseline scans to distinguish therapeutically induced stable disease from cases where the tumor growth is not perturbed by treatment.

Lessons from a multicentre retrospective study of peptide receptor radionuclide therapy combined with lanreotide for neuroendocrine tumours: a need for standardised practice

PurposePRELUDE aimed to assess use and effectiveness/safety of lanreotide autogel/depot (LAN) combined with 177Lu-DOTATOC or 177Lu-DOTATATE (LAN–peptide receptor radionuclide therapy [PRRT]) in patients with progressive neuroendocrine tumours (NETs).MethodsInternational, non-interventional, retrospective, non-comparative analysis of medical records from patients with progressive metastatic or locally advanced grade 1 or 2 gastroenteropancreatic (GEP)- or lung-NETs. The primary endpoint was progression-free survival (PFS) at end of last LAN–PRRT cycle. Secondary endpoints included PFS at last available follow-up, best overall response, objective response rate (ORR), presence and severity of diarrhoea and flushing, and safety. Post-hoc analyses were conducted to determine pre-treatment tumour growth rate (TGR) cutoffs that best predicted the ORR during treatment.ResultsForty patients were enrolled (GEP-NETs, n = 39; lung-NETs, n = 1). PFS rates were 91.7% at end of last LAN–PRRT cycle and 95.0% at last available follow-up. In the full analysis set, best overall response among patients with GEP-NETs (n = 23) was stable disease (n = 14, 60.9%), partial response (n = 8, 34.8%) and progressive disease (n = 1, 4.3%). The ORR was 27.3% at end of last LAN–PRRT cycle and 36.8% at last available follow-up. Optimal baseline TGR cutoffs for predicting ORR at these time points were 1.18% and 0.33%, respectively. At baseline, 81.0% of patients had diarrhoea or flushing; both remained stable or improved in most cases. No increased adverse drug reactions were reported.ConclusionDespite the major recruitment shortfall for the PRELUDE study, effectiveness data were encouraging in this selected population, highlighting the potential usefulness and feasibility of LAN combined with and after PRRT in patients with GEP-NETs. The study also identified challenges associated with evaluating clinical practice in a rare-disease setting and highlighted the need for standardisation of PRRT procedures.Trial registrationTrial number: NCT02788578; URL: https://clinicaltrials.gov/ct2/show/NCT02788578

Influence of pretreatment tumor growth rate on objective response of hepatocellular carcinoma treated with transarterial chemoembolization

The study aims to assess the influence of pretreatment tumor growth rate (TGR) on modified response evaluation criteria in solid tumors (mRECIST) objective response (OR) after a first session of selective transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). One hundred fifteen patients (101 men [88%], mean 65.1±10.5years [range 26-87]) with 169 tumors (mean 34.2±29.3mm [10-160]), undergoing a first session of selective TACE for the treatment of HCC between 2011 and 2016, were included. TGR was calculated as the percentage change in tumor volume per month (%/month) on imaging before treatment. TGR cut-off for prediction of OR was identified by receiver operating characteristic curve analysis. Overall 88/189 (52%) and 46/189 (27%) tumors showed complete response (CR) and partial response (PR) (OR rate 79%), while 32/189 (19%) showed stable disease (SD), and 3/189 (2%) were progressive disease (PD) on computed tomography at 1-month post-TACE. The mean pretreatment TGR was 12.0±15.4 (-3.2-90.4) %/month. TGR of tumors showing CR, PR, SD, and PD was a mean 13.2±16.4%, 12.1±15.1%, 5.3±4.5%, and 44.8±20.4%, respectively (P<0.001). The three tumors showing PD had TGR values >20%/month. TGR was significantly higher in tumors with OR (12.8±15.9% vs 5.3±4.5% in SD, P=0.009). A cut-off value of 6.5%/month had the highest predictive value of OR (AUROC 0.65±0.05, P=0.009). Pretreatment TGR is highly variable in HCC before TACE with a U-shaped distribution for the prediction of tumor response. It provides insight into tumor biology that may be used during pretreatment workup to help stratify patients.

Exploratory analysis of prognostic factors for lenvatinib in radioiodine-refractory differentiated thyroid cancer.

Multitarget kinase inhibitors (m-TKI), including lenvatinib, are now available as treatment options for radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, the optimal timing of treatment initiation with m-TKI in these patients remains to be defined. We retrospectively reviewed the clinical records of 30 consecutive patients with RR-DTC. The relationship between clinical characteristics was evaluated, including tumor growth parameters at pretreatment/post-treatment and efficacy of lenvatinib. A total of 26 patients with RR-DTC treated with lenvatinib were evaluable for response and eligible for analysis. From the results of multivariate analysis, baseline tumor size and tumor-related symptoms were independent negative prognostic factors for overall survival (OS) and progression-free survival (PFS). Pretreatment tumor growth parameters were not prognostic for either PFS or OS. Patients with RR-DTC with a high tumor burden and tumor-related symptoms had significantly worse prognosis. Greater tumor reduction after starting lenvatinib may lead to better prognosis, irrespective of pretreatment high tumor growth rate.

Clinical significance of pretreatment tumor growth rate for locally advanced non-small cell lung cancer.

Locally advanced non-small cell lung cancer (NSCLC) may exhibit significant tumor growth before the initiation of definitive chemoradiation therapy (CRT). We thus investigated the prognostic value of pretreatment tumor growth rate as measured by specific growth rate (SGR). We conducted a retrospective review of 42 patients with locally advanced NSCLC treated with definitive concurrent CRT. For each patient, we contoured the primary gross tumor volume (GTV) on the pretreatment diagnostic chest computed tomography (CT) scan and the radiation therapy (RT) planning CT scan. We then calculated SGR based on the primary GTV from each scan and the time interval between scans. We used log-rank tests and univariate Cox regression models to quantify differences in progression-free survival (PFS), overall survival (OS) and recurrence based on SGR. We divided patients into two groups for analysis: those with an SGR greater than or equal to the upper tercile value of 0.94%/day (high SGR) and those with SGR less than 0.94%/day (low SGR). Patients with high SGRs versus low SGRs experienced inferior PFS (median, 5.6 vs. 13.6 months, P=0.016), without a significant difference in OS. The inferior PFS in the high SGR group persisted on multivariate analysis [adjusted hazard ratio (HR) 2.37, 95% confidence interval (CI): 1.07-5.25, P=0.034]. The risk of distant recurrence was higher in the high SGR group (HR 2.62, 95% CI: 1.08-6.38, P=0.033), but there was no difference in the risk of locoregional recurrence between groups. Pretreatment SGR was associated with inferior PFS and distant control among patients with locally advanced NSCLC treated with concurrent CRT. Further studies in larger populations may aid in elucidating optimal SGR cut-off points for risk stratification.

Impact of tumour growth rate during preceding treatment on tumour response to regorafenib or trifluridine/tipiracil in refractory metastatic colorectal cancer

BackgroundAlthough regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have been recognised as standard treatments in metastatic colorectal cancer (mCRC), the best option remains unclear. Pretreatment tumour growth rate (TGR) is associated with radiotherapeutic efficacy in laryngeal cancer. However, no reports are available on the association between TGR during preceding treatment and the efficacy of REG or FTD/TPI.Patients and methodsWe retrospectively analysed the data of consecutive mCRC patients treated with REG or FTD/TPI and classified them into slow-growing or rapid-growing (SG or RG) groups according to TGR and emergence of new lesion (NL+) or their absence (NL−) during preceding treatment period [SG: NL− with low TGR (<0.33%/day); RG: NL+ or high TGR (≥0.33%/day)].ResultsA total of 244 patients (RG/SG, 133/111; REG/FTD/TPI, 132/112) were eligible. The RG proportion with a long duration from first-line chemotherapy and the SG proportion with elevated alkaline phosphatase were higher in REG, whereas the SG proportion with performance status 2 was higher in FTD/TPI. The disease control rates (DCRs) were similar between REG and FTD/TPI (24%/30%; OR: 0.74; p=0.44; adjusted OR: 0.73; p=0.47) in the RG, whereas the DCR was significantly higher for FTD/TPI than for REG (47%/26%; OR: 2.56; p=0.029; adjusted OR: 3.38; p=0.01) in the SG.ConclusionsTGR and NL during preceding treatment may be helpful for drug selection in refractory mCRC patients to be treated with REG or FTD/TPI. However, further studies are needed to confirm the value of TGR for drug selection.

Surgery, radiotherapy or a combined modality for jugulotympanic paraganglioma of Fisch class C and D.

To identify the risks associated with surgery, radiotherapy or a combined treatment approach for Fisch class C and D jugulotympanic paraganglioma, in order to develop an individualised approach for each patient depending on Fisch class, age, mutation presence, tumour size growth rate and presenting symptoms. A retrospective multicenter cohort study with all patient records of patients with a head and neck paraganglioma in the Radboudumc, Nijmegen and the St. Elisabeth Hospital, Tilburg, the Netherlands. Local control, cranial nerve damage, complications, function recovery. We found highest local control rates after tumour debulking with postoperative radiotherapy in case of residual tumour growth, referred to as the combined treatment group, (100%; n=19), which was significantly higher than the surgical group (82%; n=17; P=0.00), but did not differ from the radiotherapy group (90%; n=29). There were significantly less complications in the radiotherapy group, when compared to surgery (63 vs 27%; P=0.002) and the combined group (44 vs 27%; P=0.016). Furthermore,: using a logistic regression model, we found that pretreatment tumour growth was a negative predictor for post-treatment cranial nerve function recovery (OR=50.178, P=0.001), reducing the chance of symptom recovery (67.3% vs 35.7%) post-treatment. Radiotherapy should be the treatment of choice for the elderly. For younger patients, tumour debulking should be considered, with potential radiotherapy in case of residual tumour growth.

Clinical Significance of Pretreatment Tumor Growth Rate for Locally Advanced NSCLC

Clinical Significance of Pretreatment Tumor Growth Rate for Locally Advanced NSCLC

Histopathologic Features in Relation to Pretreatment Tumor Growth in Patients with Glioblastoma.

Rapid growth is a well-known property of glioblastoma (GBM); however, growth rates vary among patients. Mechanisms behind such variation have not been widely studied in human patients. We sought to investigate relationships between histopathologic features and tumor growth estimated from pretreatment magnetic resonance imaging scans. In 106 patients with GBM, 2 preoperative T1-weighted magnetic resonance imaging scans obtained at least 14 days apart were segmented to assess tumor growth. A fitted Gompertzian growth curve based on the segmented volumes divided the tumors into 2 groups: faster and slower growth than expected based on the initial tumor volume. Histopathologic features were investigated for associations with these groups, using univariable and multivariable logistic regression analyses. The presence of high cellular density and thromboses was significantly associated with radiologic growth in the multivariable analysis (P= 0.018 and 0.019, respectively), with respective odds ratios of 3.0 (95% confidence interval, 1.2-7.4) and 4.3 (95% confidence interval, 1.3-14.5) for faster growing tumors. Our findings show that high cellular density and thromboses are significant independent predictors of faster growth in human GBM. This finding underlines the importance of hypercellularity as a criterion in glioma grading. Furthermore, our findings are concordant with hypotheses suggesting hypoxia triggered by thromboses to be relevant for growth of GBM.

Does Pretreatment Tumor Growth Hold Prognostic Information for Patients with Glioblastoma?

Glioblastomas are highly aggressive and heterogeneous tumors, both in terms of patient outcome and molecular profile. Magnetic resonance imaging of tumor growth could potentially reveal new insights about tumor biology noninvasively. The aim of this exploratory retrospective study was to investigate the prognostic potential of pretreatment growth rate of glioblastomas, after controlling for known prognostic factors. A growth model derived from clinical pretreatment postcontrast T1-weighted magnetic resonance imaging images was used to divide 106 glioblastoma patients into 2 groups. The "faster growth" group had tumors growing faster than expected based on their volume at diagnosis, whereas the "slower growth" group had tumors growing slower than expected. Associations between tumor growth and survival were examined by the use of multivariable Cox regression and logistic regression. None of the known prognostic factors were significantly associated with tumor growth. An extended multivariable Cox model showed that during the first 12 months of follow-up, there was no significant difference in survival between faster and slower growing tumors. Beyond 12 months' follow-up, however, there was a significant, independent survival benefit in having a tumor with slower pretreatment growth. In a multiple logistic regression model including patients receiving both radiotherapy and chemotherapy (n= 82), slower pre-treatment growth of the tumor was shown to be a significant predictor of 2-year survival (odds ratio 4.4). Pretreatment glioblastoma growth harbors prognostic information. Patients with slower growing tumors have higher odds of survival beyond 2 years, adjusted for other prognostic factors.

Pretreatment growth rate as a predictor of tumor control following Gamma Knife radiosurgery for sporadic vestibular schwannoma.

OBJECTIVE Over the last 30 years, stereotactic radiosurgery (SRS) has become an established noninvasive treatment alternative for small- to medium-sized vestibular schwannoma (VS). This study aims to further define long-term SRS tumor control in patients with documented pretreatment tumor growth for whom conservative observation failed. METHODS A prospective clinical database was queried, and patients with sporadic VS who elected initial observation and subsequently underwent SRS after documented tumor growth between 2004 and 2014 were identified. Posttreatment tumor growth or shrinkage was determined by a ≥ 2-mm increase or decrease in maximum linear dimension, respectively. RESULTS Sixty-eight patients met study inclusion criteria. The median pre- and posttreatment observation periods were 16 and 43.5 months, respectively. The median dose to the tumor margin was 13 Gy (range 12-14 Gy), and the median maximum dose was 26 Gy (range 24-28 Gy). At the time of treatment, 59 tumors exhibited extracanalicular (EC) extension, and 9 were intracanalicular (IC). Of the 59 EC VSs, 50 (85%) remained stable or decreased in size following treatment, and 9 (15%) enlarged by > 2 mm. Among EC tumors, the median pretreatment tumor growth rate was 2.08 mm/year for tumors that decreased or were stable, compared with 3.26 mm/year for tumors that grew following SRS (p = 0.009). Patients who demonstrated a pretreatment growth rate of < 2.5 mm/year exhibited a 97% tumor control rate, compared with 69% for those demonstrating ≥ 2.5 mm/year of growth prior to SRS (p = 0.007). No other analyzed variables were found to predict tumor growth following SRS. CONCLUSIONS Overall, SRS administered using a marginal dose between 12-14 Gy is highly effective in treating VSs in which initial observation fails. Tumor control is achieved in 97% of VSs that exhibit slow (< 2.5 mm/year) pretreatment growth; however, SRS is less successful in treating tumors exhibiting rapid growth (≥ 2.5 mm/year).

Pretreatment Growth Rate as a Predictor of Tumor Control Following Gamma Knife Radiosurgery for Sporadic Vestibular Schwannoma

OBJECTIVE Over the last 30 years, stereotactic radiosurgery (SRS) has become an established noninvasive treatment alternative for small- to medium-sized vestibular schwannoma (VS). This study aims to further define long-term SRS tumor control in patients with documented pretreatment tumor growth for whom conservative observation failed. METHODS A prospective clinical database was queried, and patients with sporadic VS who elected initial observation and subsequently underwent SRS after documented tumor growth between 2004 and 2014 were identified. Posttreatment tumor growth or shrinkage was determined by a ≥ 2-mm increase or decrease in maximum linear dimension, respectively. RESULTS Sixty-eight patients met study inclusion criteria. The median pre- and posttreatment observation periods were 16 and 43.5 months, respectively. The median dose to the tumor margin was 13 Gy (range 12-14 Gy), and the median maximum dose was 26 Gy (range 24-28 Gy). At the time of treatment, 59 tumors exhibited extracanalicular (EC) extension, and 9 were intracanalicular (IC). Of the 59 EC VSs, 50 (85%) remained stable or decreased in size following treatment, and 9 (15%) enlarged by > 2 mm. Among EC tumors, the median pretreatment tumor growth rate was 2.08 mm/year for tumors that decreased or were stable, compared with 3.26 mm/year for tumors that grew following SRS (p = 0.009). Patients who demonstrated a pretreatment growth rate of < 2.5 mm/year exhibited a 97% tumor control rate, compared with 69% for those demonstrating ≥ 2.5 mm/year of growth prior to SRS (p = 0.007). No other analyzed variables were found to predict tumor growth following SRS. CONCLUSIONS Overall, SRS administered using a marginal dose between 12-14 Gy is highly effective in treating VSs in which initial observation fails. Tumor control is achieved in 97% of VSs that exhibit slow (< 2.5 mm/year) pretreatment growth; however, SRS is less successful in treating tumors exhibiting rapid growth (≥ 2.5 mm/year).

Effect of Stereotactic Body Radiotherapy on the Growth Kinetics and Enhancement Pattern of Primary Renal Tumors.

The objective of our study was to assess the growth rate and enhancement of renal masses before and after treatment with stereotactic body radiotherapy (SBRT). This retrospective study included all patients with renal masses who underwent SBRT during a 5-year period. Orthogonal measurements of renal masses were obtained on pre- and posttreatment CT or MRI. Pre- and posttreatment growth rates were compared for renal mass diameter and volume using the t test. Pre- and posttreatment tumor enhancement values were compared for tumors that underwent multiphasic contrast-enhanced MRI. Forty patients underwent SBRT for the treatment of 41 renal tumors: clear cell renal cell carcinomas (RCCs) (n = 16), papillary RCCs (n = 6), oncocytic neoplasms (n = 8), unclassified RCCs (n = 2), urothelial carcinoma (n = 1), and no pathologic diagnosis (n = 8). The mean maximum tumor diameter before treatment was 3.9 cm (range, 1.6-8.3 cm). Three hundred thirty-eight pre- and posttreatment imaging studies were analyzed: 214 MRI studies and 124 CT studies. The mean pre- and posttreatment lengths of observation were 416 days (range, 2-1800 days) and 561 days (83-1366 days), respectively. The mean pretreatment tumor growth rate of 0.68 cm/y decreased to -0.37 cm/y post treatment (p < 0.0001), and the mean tumor volume growth rate of 21.2 cm(3)/y before treatment decreased to -5.35 cm(3)/y after treatment (p = 0.002). Local control-defined as less than 5 mm of growth-was achieved in 38 of 41 (92.7%) tumors. The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 showed progression in one tumor (2.4%), stability in 31 tumors (75.6%), partial response in eight tumors (19.5%), and complete response in one tumor (2.4%). No statistically significant change in tumor enhancement was shown (mean follow-up, 142 days; range, 7-581 days). Renal tumors treated with SBRT show statistically significant reductions in growth rate and tumor size after treatment but do not show statistically significant differences in enhancement in the initial (mean, 142 days) posttreatment period.