Radiation Dose and Fractionation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns

Farrell, Matthew J.; Yahya, Jehan; Degnin, Catherine; Chen, Yiyi; Holland, John M.; Henderson, M.; Jaboin, Jerry J.; Harkenrider, Matthew M.; Thomas, Charles R.; Mitin, Timur

doi:10.1016/j.cllc.2018.08.015

Cited by 38 publications

(44 citation statements)

References 17 publications

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“…But then, the CONVERT trial showed no significant difference in survival and toxicity between twice-daily (45Gy in 30 twice-daily fractions of 1.5Gy over 19 days) and once-daily (66Gy in 33 daily fractions of 2Gy over 45 days) concurrent chemoradiotherapy in LS-SCLC patients, using modern conformal radiotherapy techniques [23]. In fact, considering the convenience for patients and logistical ease [25], we preferred once-daily therapy in this study.…”

Section: Discussionmentioning

confidence: 83%

Concurrent or Sequential Chemoradiotherapy after 3-4 Cycles Induction Chemotherapy for LS-SCLC with Bulky Tumor

Zhao

Zhang

et al. 2020

J. Cancer

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The current study was to compare the efficacy and safety between concurrent and sequential chemoradiotherapy after 3-4 cycles of induction chemotherapy for limited-stage small-cell lung cancer (LS-SCLC) with bulky tumor. From July 2012 to September 2015, a total of 68 patients with stage IIIA and IIIB SCLC who had completed 3-4 cycles of etoposide plus cisplatin/carboplatin and achieved clinical complete response (cCR) or clinical partial response (cPR) were randomized into the two groups equally. The concurrent group received radiotherapy combined with oral etoposide and cisplatin and the sequential group received sequential chemoradiotherapy. Thoracic radiotherapy was performed using intensity-modulated radiation therapy (IMRT) with 95% PTV 60Gy/30 times. After completing chemoradiotherapy, patients received prophylactic cranial irradiation. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and toxicity. The median follow-up time was 63.3 months (95% confidence interval [CI], 50.8-75.8). Better PFS and OS were observed in concurrent group (median PFS, 26.0 months [95% CI, 9.0-43.0] versus 13.1 months [95%CI, 9.7-16.6], p=0.023; median OS, 35.0 months [95% CI, 25.4-44.6] versus 22.0 months [95% CI, 17.0-27.1], p=0.015). There was no significant difference in the incidence of radiation esophagitis and radiation pneumonitis between the two groups (p=0.795, p=0.525). This study demonstrated that after the completion of 3-4 cycles of chemotherapy with a remission, concurrent chemoradiotherapy with oral etoposide and cisplatin improved survival compared with sequential chemoradiotherapy in LS-SCLC with bulky tumor. ClinicalTrials.gov Identifier: NCT01745445.

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Section: Discussionmentioning

confidence: 83%

Concurrent or Sequential Chemoradiotherapy after 3-4 Cycles Induction Chemotherapy for LS-SCLC with Bulky Tumor

Zhao

Zhang

et al. 2020

J. Cancer

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Section: Discussionmentioning

confidence: 99%

“…Another utility of the modeling framework is in translational simulation scenarios to evaluate dose fractionation of ADC therapies, which may have not been adopted by clinicians due to toxicity concerns seen with other therapies. 35 The model sensitivity analyses provided mechanistic insight into how ADCs and tumor properties can be stratified to predict population responses. For example, sensitivity analysis led to a counterintuitive hypothesis that lower ADC affinity to the target increases tumor targeting and killing.…”

Section: Intra-tumor Distribution Of Adcsmentioning

confidence: 99%

Mechanistic Modeling of Intra‐Tumor Spatial Distribution of Antibody‐Drug Conjugates: Insights into Dosing Strategies in Oncology

Weddell

Chiney

Bhatnagar

et al. 2020

Clinical Translational Sci

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Antibody drug conjugates (ADCs) provide targeted delivery of cytotoxic agents directly inside tumor cells. However, many ADCs targeting solid tumors have exhibited limited clinical efficacy, in part, due to insufficient penetration within tumors. To better understand the relationship between ADC tumor penetration and efficacy, previously applied Krogh cylinder models that explore tumor growth dynamics following ADC administration in preclinical species were expanded to a clinical framework by integrating clinical pharmacokinetics, tumor penetration, and tumor growth inhibition. The objective of this framework is to link ADC tumor penetration and distribution to clinical efficacy. The model was validated by comparing virtual patient population simulations to observed overall response rates from trastuzumab‐DM1 treated patients with metastatic breast cancer. To capture clinical outcomes, we expanded upon previous Krogh cylinder models to include the additional mechanism of heterogeneous tumor growth inhibition spatially across the tumor. This expansion mechanistically captures clinical response rates by describing heterogeneous ADC binding and tumor cell killing; high binding and tumor cell death close to capillaries vs. low binding, and high tumor cell proliferation far from capillaries. Sensitivity analyses suggest that clinical efficacy could be optimized through dose fractionation, and that clinical efficacy is primarily dependent on the ADC‐target affinity, payload potency, and tumor growth rate. This work offers a mechanistic basis to predict and optimize ADC clinical efficacy for solid tumors, allowing dosing strategy optimization to improve patient outcomes.

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“…In an American survey conducted before the CONVERT trial publication, 60% (n = 184) of clinicians preferred administering OD radiotherapy, mainly (130/184: 71%) because it is more convenient for patients [7]. It should however be emphasised that most departments only treat small numbers of LS-SCLC patients each year.…”

Section: Discussionmentioning

confidence: 99%

“…Hyperfractionated radiotherapy combined with chemotherapy yields better overall survival (OS) compared with standard radiotherapy [4]. However, hyperfractionated radiotherapy schedules have not been widely adopted in routine practice due to limitations in the design of previous studies [4,5], logistical issues and an increase in acute toxicity [6,7]. The CONVERT trial is a multi-centre phase III trial (NCT00433563) that randomly assigned LS-SCLC patients, with Eastern Cooperative Oncology Group performance score 0-2, to receive either twice-daily (BD; 45 Gy in 30 fractions) or oncedaily (OD; 66 Gy in 33 fractions) radiotherapy starting with the second https://doi.org/10.1016/j.lungcan.…”

Section: Introductionmentioning

confidence: 99%

Current management of limited-stage SCLC and CONVERT trial impact: Results of the EORTC Lung Cancer Group survey

et al. 2019

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Radiation Dose and Fractionation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns

Cited by 38 publications

References 17 publications

Concurrent or Sequential Chemoradiotherapy after 3-4 Cycles Induction Chemotherapy for LS-SCLC with Bulky Tumor

Concurrent or Sequential Chemoradiotherapy after 3-4 Cycles Induction Chemotherapy for LS-SCLC with Bulky Tumor

Mechanistic Modeling of Intra‐Tumor Spatial Distribution of Antibody‐Drug Conjugates: Insights into Dosing Strategies in Oncology

Current management of limited-stage SCLC and CONVERT trial impact: Results of the EORTC Lung Cancer Group survey

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