Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): A meta-analysis of randomized trials

Budach, Wilfried; Bölke, Edwin; Kammers, Kai; Gerber, Peter Arne; Orth, Klaus; Gripp, Stephan; Matuschek, Christiane

doi:10.1016/j.radonc.2015.10.014

Cited by 97 publications

(52 citation statements)

References 24 publications

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“…Combined modality therapy consists of surgery and radiotherapy with or without chemotherapy or molecular targeted therapy [110][111][112]. No matter what the therapeutic intervention, however, HNSCC is still associated with a high rate of recurrence [113,114].…”

Section: Carbon Ion Irradiation Counteracts Cancer Stem Cells' Migratmentioning

confidence: 99%

The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

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Aim: Cancer stem cells (CSCs) exhibited an excessive migratory and invasive potential. Melatonin may inhibit multiple crucial signals associated with tumor stem cell self-renewal, viability, invasiveness, tumor growth, and therapy resistance. Carbon ion irradiation may be a promising therapeutic modality in both non-stem-like and stem-like tumor cells in contrast to photon irradiation. A comprehensive understanding of the mechanisms and molecular pathways associated with invasive properties of CSCs is essential in developing novel treatment options for cancer therapy that target CSCs. Materials and methods:A systematic review of the existing literature was conducted using the following search terms: 'melatonin', 'X-ray irradiation', 'charged particle irradiation', 'carbon ion irradiation', 'cancer stem cells', 'tumor-initiating cells' and 'cancer stem-like cells'. The search used PubMed and spanned the period from January 2000 to December 2016. Conclusion:Cancer stem cells possess the capacity of self-renewal and pluripotency, generating all cells within a tumor, and are responsible for tumor growth, therapy resistance and metastasis. Melatonin attenuated AKT activation, EZH2 S21 phosphorylation, EZH2-STAT3 interactions and altered histone modifications to reduce tumor initiation and propagation of brain tumor stem cells (BTSC). Melatonin increases the efficacy of chemotherapeutic agents, targeting both the tumor bulk and BTSCs through the regulation of the expression and function of the ABCG2/BCRP transporter by inducing the methylation of its promoter. Melatonin treatment induced cell death with ultrastructural characteristics of autophagy. Breast cancer stem cells (BCSCs) are responsive to melatonin treatment by way of reducing the viability and the invasiveness of breast cancer mammospheres as well as regulating the expression of OCT4, N-cadherin and vimentin proteins associated with epithelial mesenchymal transition in BCSCs. Carbon irradiation is effective in brain tumor stem cell (BTSC) elimination with relative biologic effectiveness (RBE) in the range of 1.87-3.44. Carbon ion irradiation may be a promising therapeutic modality because it reduces migration and invasion processes in both head and neck squamous cell carcinoma and cancer stem cells in contrast to photon irradiation. Low LET X-ray irradiation may essentially eradicate the non-stem-like tumor cells, consequently the radioresistant cancer stem-like cell population is obviously enriched. In contrast, carbon ion irradiation may eradicate both non-stemlike and stem-like tumor cells at the same time. Carbon ion irradiation is a promising tool to eradicate putative colon cancer stem-like cells. Further investigation to elucidate the mechanisms and molecular pathways involved in cancer stem cells particularly associated with melatonin and carbon ion irradiation certainly is warranted.

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Section: Carbon Ion Irradiation Counteracts Cancer Stem Cells' Migratmentioning

confidence: 99%

The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

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“…In several phase III trials, combination of docetaxel, cisplatin (CDDP), and 5‐fluorouracil (TPF) improved clinical response and survival compared with CDDP and 5‐fluorouracil (PF) alone, and this regimen is now considered the accepted standard of care for IC . However, because no study featured CRT with CDDP in the control arm, the addition of IC (TPF) to CDDP‐based CCRT (sequential CRT) has not been shown to be superior to CDDP‐based CCRT alone . More importantly, discussion continues over whether sequential CRT can be safely administered and whether its compliance can be assured given the significant toxicities of induction TPF.…”

Section: Introductionmentioning

confidence: 99%

A multicenter phase II trial of paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy in patients with unresectable locally advanced squamous cell carcinoma of the head and neck

et al. 2020

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Background Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA‐SCCHN. Methods Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration‐time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2, 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%. Results Thirty‐five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment‐related death was seen. Conclusions PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA‐SCCHN.

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“…Like the aforementioned American studies, each of these international trials may be statistically underpowered, again highlighting the need for larger numbers of subjects. Even meta‐analyses that pool trials and incorporate roughly 1000 patients have demonstrated no OS improvement with induction chemotherapy …”

Section: Discussionmentioning

confidence: 99%

“…The NCDB offers one of the largest populations presently available to answer this question, including sizeable numbers with advanced disease, allowing us to overcome this limitation. Our analysis captured 2378 individuals with T4 disease and 7037 with N2b to N3 disease, comparing favorably to the 59 and 35 subjects with T4 disease and the 285 and 118 patients with N2a to N3 disease in the DeCIDE and PARADIGM trials, respectively, and to the approximately 1000 subjects with varying stages included in the meta‐analyses . Thus, even though our study of the NCDB is nonrandomized, the database offers the advantage of large numbers of subjects with advanced disease, thereby overcoming the key shortcoming of published trials and pooled analyses addressing this question.…”

Section: Discussionmentioning

confidence: 99%

Survival impact of induction chemotherapy in advanced head and neck cancer: A National Cancer Database analysis

et al. 2017

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Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): A meta-analysis of randomized trials

Abstract: Additional induction CHX with TPF before RT-CHX does not improve OS and PFS in locally advanced HNSCC compared to definite RT-CHX.

Cited by 97 publications

References 24 publications

The impact of melatonin and carbon ion irradiation on cancer stem cells

The impact of melatonin and carbon ion irradiation on cancer stem cells

A multicenter phase II trial of paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy in patients with unresectable locally advanced squamous cell carcinoma of the head and neck

Survival impact of induction chemotherapy in advanced head and neck cancer: A National Cancer Database analysis

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