Radiation Dose Escalation in Accelerated Hyperfractionated Radiotherapy for Stage III Non-small-cell Lung Cancer

Wada, Kentaro; Kishi, Noriko; Kanayama, Naoyuki; Hirata, Takero; Morimoto, Masahiro; Koyama, Koji; Imamura, Fumio; Teshima, Teruki; Ogawa, Kazuhiko

doi:10.21873/anticanres.12941

Cited by 7 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunophenotyping of peripheral blood lymphocytes of tumor patients by multicolor flow cytometry has been found to be useful for predicting outcome and detecting immunomodulation by ionizing irradiation [33, 34]. Similar to studies with mammary and prostate carcinomas [35], RCT also negatively impacts on the B cell compartment of the NSCLC patient, due to the sensitivity of B cells towards radiotherapy [36].…”

Section: Discussionmentioning

confidence: 99%

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study

Kokowski

Stangl²,

Seier³

et al. 2019

Strahlenther Onkol

View full text Add to dashboard Cite

BackgroundMembrane heat shock protein 70 (mHsp70) is indicative of high-risk tumors and serves as a tumor-specific target for natural killer (NK) cells stimulated with Hsp70 peptide (TKD) and Interleukin(IL)-2. Radiochemotherapy (RCT), mHsp70-targeting NK cells, and programmed death(PD)-1 inhibition were combined to improve the efficacy of tumor-specific immune cells in a non-small cell lung carcinoma (NSCLC) patient.PatientFollowing simultaneous RCT (64.8 Gy), a patient with inoperable NSCLC (cT4, cN3, cM0, stage IIIb) was treated with 4 cycles of autologous ex vivo TKD/IL-2-activated NK cells and the PD-1 antibody nivolumab as a second-line therapy. Blood samples were taken for immunophenotyping during the course of therapy.ResultsAdoptive transfer of ex vivo TKD/IL-2-activated NK cells after RCT combined with PD-1 blockade is well tolerated and results in superior overall survival (OS). No viable tumor cells but a massive immune cell infiltration in fibrotic tissue was detected after therapy. Neither tumor progression nor distant metastases were detectable by CT scanning 33 months after diagnosis. Therapy response was associated with significantly increased CD3−/NKG2D+/CD94+ NK cell counts, elevated CD8+ to CD4+ T cell and CD3−/CD56bright to CD3−/CD56dim NK cell ratios, and significantly reduced regulatory T cells (Tregs) in the peripheral blood.ConclusionA combined therapy consisting of RCT, mHsp70-targeting NK cells, and PD-1 antibody inhibition is well tolerated, induces anti-tumor immunity, and results in long-term tumor control in one patient with advanced NSCLC. Further, randomized studies are necessary to confirm the efficacy of this combination therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study

Kokowski

Stangl²,

Seier³

et al. 2019

Strahlenther Onkol

View full text Add to dashboard Cite

show abstract

“…Radiotherapy alone or in combination with systemic therapies is commonly used for treating locally advanced lung cancers (2). As the prognosis of these patients is often limited, considerable research is carried out to improve their outcomes (9)(10)(11)(12)(13). If radiotherapy is administered, high doses are often required, particularly if the treatment approach is considered curative.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Characteristics of Symptomatic Pneumonitis After Radiotherapy of Patients With Locally Advanced Lung Cancer

et al. 2019

View full text Add to dashboard Cite

Background/Aim: Radiotherapy of locally advanced lung cancer often requires high doses potentially leading to pneumonitis. This study evaluated the rate of symptomatic pneumonitis and characteristics in these patients. Patients and Methods: This study included 278 patients irradiated for locally advanced lung cancer between 2016 and 2019. In patients experiencing symptomatic pneumonitis, patient and treatment characteristics were analyzed. Results: Pneumonitis was diagnosed in 21 patients (7.6%) after a median of 9 (1-23) weeks. Ipsilateral lungs received mean doses >13 Gy in 21 (100%) and >20 Gy in 15 patients (71.4%). Seventeen patients (81.0%) received chemotherapy and/or immunotherapy, 12 (57.1%) had significant cardiovascular disease (all 21 patients had risk factors), 11 (52.4%) were heavy smokers (≥40 pack years), 7 (33.3%) were aged ≥74 years, 5 (23.8%) had chronic inflammatory disease and 4 (19.0%) had previous tumors. Conclusion: Overall pneumonitis rate was 7.6%. Frequent characteristics included high mean lung doses, systemic treatment, cardiovascular disease (and risk factors), heavy smoking, older age, chronic inflammatory disease and history of a previous tumor.

show abstract

“…Although the efficacy of dose escalation is unclear, treatment using accelerated hyperfractionated radiotherapy (AHRT) was previously shown to improve local control and overall survival (OS) (2)(3)(4). A phase 2 study and a propensity matched analysis showed that accelerated hyperfractionated concurrent chemoradiotherapy (AH-CCRT) (64 Gy in 40 fractions twice daily) resulted in an excellent response rate and OS (5,6).…”

mentioning

confidence: 99%

Predictors of Acute Radiation Esophagitis in Non-small Cell Lung Cancer Patients Treated With Accelerated Hyperfractionated Chemoradiotherapy

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background/Aim: To identify the clinical and dosimetric predictors of severe acute radiation esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with accelerated hyperfractionated concurrent chemoradiotherapy (AH-CCRT) with concomitant boost technique. Patients and Methods: A total of 159 patients who underwent AH-CCRT (64 Gy in 40 fractions twice daily) were retrospectively identified. Severe RE was designated as grade 3 or higher according to the Common Terminology Criteria for Adverse Events, version 4.0. Results: The incidence rate of grade 3 RE was 15.1% (24/159). The multivariate analysis that incorporated the Eastern Cooperative Oncology Group performance status (ECOG PS, ≥1 vs. 0) and the relative esophagus volume irradiated with at least 60 Gy (V 60) was optimal. Patients with a V 60 of ≥15% had a 37.8% risk of grade 3 RE compared to a 6.1% risk among those with a V 60 of <15%. Conclusion: ECOG PS (≥1 vs. 0) and the V 60 were found to be significant risk factors for severe RE in NSCLC patients who underwent AH-CCRT. Non-small cell lung cancer (NSCLC) is a major cause of death worldwide. The standard of care for patients with locally 491 This study was presented in part as poster at the 59th Annual Meeting of the

show abstract

Radiation Dose Escalation in Accelerated Hyperfractionated Radiotherapy for Stage III Non-small-cell Lung Cancer

Cited by 7 publications

References 0 publications

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study

Prevalence and Characteristics of Symptomatic Pneumonitis After Radiotherapy of Patients With Locally Advanced Lung Cancer

Predictors of Acute Radiation Esophagitis in Non-small Cell Lung Cancer Patients Treated With Accelerated Hyperfractionated Chemoradiotherapy

Contact Info

Product

Resources

About