Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Werner‐Wasik, Maria; Swann, Ruth; Bradley, Jeffrey D.; Graham, Mary V.; Emami, Bahman; Purdy, James A.; Sause, William T.

doi:10.1016/j.ijrobp.2007.06.034

Cited by 97 publications

(53 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GTV1 before RT trended to be associated with OS in univariate analysis which amends current literature showing strong evidence for a prognostic significance of tumor volume detected before RT (13)(14)(15)(16)22) or chemotherapy of NSCLC (23). Koo et al (14) for instance reported a trend for inferior survival outcome in patients with poor tumor volume reduction during CCRT of Decrease Increase Total GTV1 to GTV2 Decrease 15 10 25 Increase 0 2 2 Total 15 12 27 OPN, osteopontin.…”

Section: Discussionsupporting

confidence: 52%

“…Furthermore, there is strong evidence in the literature that GTV is a potential prognostic factor in conformal RT of NSCLC (13)(14)(15)(16)21).…”

Section: Discussionmentioning

confidence: 99%

“…However, the prognostic role of a segregation of lymph nodes from primary tumors remains controversial (14,15,21).…”

Section: Opn T0 To T1 ----------------------------------------------mentioning

confidence: 99%

“…higher basal OPN plasma levels in patients with larger GTV) in a series of 69 NSCLC M0-stage patients treated with definite CCRT. In the literature, there is evidence that GTV has a clinically relevant impact on overall survival (OS) after CCRT of NSCLC (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer

et al. 2016

View full text Add to dashboard Cite

Abstract. The prognostic quality of increased osteopontin (OPN) plasma levels has been demonstrated for the chemotherapy and surgery of lung cancer. There is also evidence in the literature that tumor volume impacts prognosis in definitive radiotherapy (RT) of (lung) cancer. We previously demonstrated that elevated plasma levels of OPN before, and increasing OPN plasma levels after RT significantly correlate with survival and outcome after curative-intent RT of non-small-cell lung cancer (NSCLC). Tumor volume was also associated with prognosis. The present prospective clinical study investigated the prognostic interrelation of OPN plasma levels and tumor volume and their changes in the radical RT of NSCLC. We evaluated a subset of patients (n=27) with inoperable, non-metastasized NSCLC of the previously published patient collective. Patients were treated with radical radiochemotherapy (2 Gy ad 66 Gy). OPN plasma concentrations were determined by ELISA before (t0), at the end (t1), and 4 weeks after RT (t2). GTV was delineated PET-and CT-correlated before RT (GTV1) and after 40 Gy (GTV2). The course of OPN during and after RT and the change of GTV during RT was monitored over time and correlated with prognosis. Median GTV2 after 40 Gy (63 ml) was significantly lower than pre-RT GTV1 (90 ml, P<0.0001). Median OPN before (t0), at the end of (t1) and four weeks after RT (t2) was 846, 777 and 624 ng/ml and not significantly different. GTV significantly declined by 39 ml during RT (P<0.0001) and OPN non-significantly decreased by 56 ng/ml during (t0 to t1) and by 54 ng/ml after RT (t1 to t2). No correlations were determined between absolute OPN and GTV values or their relative changes during RT. In univariate analysis, only GTV2 significantly predicted overall survival (OS, P=0.03). In multivariate analysis, both OPN t1 (P<0.001) and GTV2 (P= 0.001) remained significant predictors of OS. Relative OPN plasma level changes after (t1 to t2) and GTV changes during RT (GTV 1 to GTV 2) significantly predicted OS (P=0.02). The combination of absolute GTV values before RT (GTV1) and GTV changes during RT (GTV1 to 2) were significantly associated with OS in both uni-and multivariate analysis (P=0.03). The combination of absolute OPN plasma levels and their changes with GTV and its changes did not reach statistical significance. The lack of a significant correlation between OPN and GTV together with the finding that OPN and GTV remained independent predictors of survival outcome but were not associated with OS in combination supports the hypothesis that tumor volume (GTV) and OPN plasma levels (both their changes and absolute values) are not interrelated in terms of prognosis but do possess each parameter separately, a prognostic quality in the radical RT of NSCLC which justifies further prospective studies to validate these results.

show abstract

Section: Discussionsupporting

confidence: 52%

“…Furthermore, there is strong evidence in the literature that GTV is a potential prognostic factor in conformal RT of NSCLC (13)(14)(15)(16)21).…”

Section: Discussionmentioning

confidence: 99%

“…However, the prognostic role of a segregation of lymph nodes from primary tumors remains controversial (14,15,21).…”

Section: Opn T0 To T1 ----------------------------------------------mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…[9][10][11][28][29][30][31][32]. The coupling between the tumor dynamics and the immune response is obtained mathematically by the product of two mechanisms.…”

Section: Biological Hypotheses and Mathematical Interpretationsmentioning

confidence: 99%

Mathematical Modeling of Cancer Immunotherapy and Its Synergy with Radiotherapy

et al. 2016

View full text Add to dashboard Cite

Combining radiotherapy with immune checkpoint blockade may offer considerable therapeutic impact if the immunosuppressive nature of the tumor microenvironment (TME) can be relieved. In this study, we used mathematical models, which can illustrate the potential synergism between immune checkpoint inhibitors and radiotherapy. A discrete-time pharmacodynamic model of the combination of radiotherapy with inhibitors of the PD1-PDL1 axis and/or the CTLA4 pathway is described. This mathematical framework describes how a growing tumor first elicits and then inhibits an antitumor immune response. This antitumor immune response is described by a primary and a secondary (or memory) response. The primary immune response appears first and is inhibited by the PD1-PDL1 axis, whereas the secondary immune response happens next and is inhibited by the CTLA4 pathway. The effects of irradiation are described by a modified version of the linearquadratic model. This modeling offers an explanation for the reported biphasic relationship between the size of a tumor and its immunogenicity, as measured by the abscopal effect (an offtarget immune response). Furthermore, it explains why discontinuing immunotherapy may result in either tumor recurrence or a durably sustained response. Finally, it describes how synchronizing immunotherapy and radiotherapy can produce synergies. The ability of the model to forecast pharmacodynamic endpoints was validated retrospectively by checking that it could describe data from experimental studies, which investigated the combination of radiotherapy with immune checkpoint inhibitors. In summary, a model such as this could be further used as a simulation tool to facilitate decision making about optimal scheduling of immunotherapy with radiotherapy and perhaps other types of anticancer therapies. Cancer Res; 76(17); 4931-40. Ó2016 AACR.

show abstract

Quality of Life Analysis of a Radiation Dose–Escalation Study of Patients With Non–Small-Cell Lung Cancer

et al. 2016

Self Cite

View full text Add to dashboard Cite

Importance A recent randomized radiation dose escalation trial in unresectable stage III NSCLC showed a lower survival in the high-dose arm (74Gy vs. 60Gy) with concurrent chemotherapy. Quality of life (QOL), an important secondary endpoint, is presented here. Objective The primary QOL hypothesis predicted a clinically meaningful decline (CMD) in QOL via the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) in the high-dose RT-arm at 3 months. Design RTOG 0617 was a randomized phase III study (conducted from Nov 2007 to Nov 2011) in stage III NSCLC using a 2×2 factorial design and stratified by histology, PET staging, performance status and radiation technique (3D-conformal RT [3DCRT] vs. intensity-modulated radiation [IMRT]). Setting 185 institutions in the USA and Canada. Participants Of 424 eligible stage III NSCLC patients randomized, 360 (85%) consented to QOL, of whom 313 (88%) completed baseline QOL assessments. Intervention for Clinical Trials 74Gy vs. 60Gy with concurrent and consolidation carboplatin/paclitaxel +/− cetuximab. Main Outcomes and Measures QOL was collected prospectively via FACT-Trial Outcome Index (FACT-TOI), equaling Physical-Well-Being (PWB) + Functional-Well-Being (FWB) + Lung Cancer Subscale (LCS). Data are presented at baseline & 3 and 12 months via minimal clinically meaningful changes of >=2 points for PWB, FWB or LCS or >=5 points for TOI. Results Patient demographics and baseline QOL scores were comparable between the 74Gy and 60Gy arms. Two-hundred-nineteen (72%) of living patients who completed QOL at baseline did so at 3 months and 137 (57%) of living patients did so at 12 months. Significantly more patients on 74Gy arm had clinically meaningful decline in FACT-LCS at 3 months than on the 60Gy arm (45% vs. 30%, p=0.02). At 12 months, fewer patients who received IMRT (vs 3DCRT) had clinically meaningful decline in FACT-LCS (21% vs 46%, p=0.003). Baseline FACT-TOI was associated with overall survival in multivariate analysis. Conclusions and Relevance Despite few differences in provider-reported toxicity between arms, QOL analysis demonstrated a clinically meaningful decline in QOL on the 74Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival. Study registered with ClinicalTrials.gov, number NCT00533949.

show abstract

Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Cited by 97 publications

References 13 publications

The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer

The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer

Mathematical Modeling of Cancer Immunotherapy and Its Synergy with Radiotherapy

Quality of Life Analysis of a Radiation Dose–Escalation Study of Patients With Non–Small-Cell Lung Cancer

Contact Info

Product

Resources

About