Laryngeal cancer recurrence : prognostic factors and management

Forskningsoutput: AvhandlingDoktorsavhandlingSamling av artiklar

Sammanfattning

Laryngeal cancer is one of the most common head and neck cancers. The treatment of laryngeal squamous cell carcinoma (LSCC) has evolved towards non-surgical treatment, namely radiotherapy and chemoradiotherapy. However, the treatment outcome of LSCC has not improved. LSCC recurs in up to 30% of patients. The current knowledge on prognostic factors for recurrence is too limited to aid in treatment decisions. In this study, the treatment outcome and recurrences of 342 patients treated with curative intent for LSCC at the Finnish university hospitals during 2001-2005 were evaluated. The outcome of T1a glottic carcinomas was excellent; none of the patients died of LSCC. The results for T2 carcinomas was worse than expected; the 5-year disease-specific survival for glottic and supraglottic carcinomas in this group was 78% and 54%, respectively. The results for T3-4 carcinomas were comparable with those reported in the literature. Recurrence was observed in 22% of patients and 91% of the recurrences occured within 36 months of treatment. None of the patients with glottic T1a tumors had recurrence after 36 months, which questions the feasibility of routine 5-year follow-up for this patient group. WHO performance status >0, presence of neck metastases, and non-surgical primary treatment were significant independent predictors of recurrence. Local recurrence of glottic LSCC could be successfully salvaged. Regional or distant recurrence and any recurrence of supraglottic LSCC carried a poor prognosis. These results underline the importance of sufficiently aggressive primary treatment, particularly for supraglottic LSCC. Some LSCCs persist or recur after non-surgical treatment. Currently, there are no validated tools to identify these tumors. In this study, the expression of survivin, an inhibitor of apoptosis, Wrap53β, a protein associated with DNA double-strand break repair and telomere elongation, and p16INK4a, a surrogate marker for human papillomavirus infection, and their relation to treatment response and prognosis was investigated in LSCC tissue samples of 149 Finnish and Swedish T2-3N0M0 glottic LSCC patients treated with radiotherapy or chemoradiotherapy. Survivin showed no predictive or prognostic value. Cytoplasmic expression of Wrap53β was associated with reduced disease-free survival and overall survival. P16INK4a expression was rare in LSCC patients (7%) and more common among patients under the age of 60. In this younger patient group, none of the patients with p16INK4a expression experienced tumor recurrence. Surgery is the only standard salvage option for patients with LSCC recurrence after non-surgical therapy. Other salvage options are being investigated, one of which is boron neutron capture therapy (BNCT). In BNCT, non-radioactive boron, B10, commonly in a compound of boronophenylalanine-fructose (BPA-F), is infused intravenously. This substance has a tendency to accumulate preferably in tumor cells. After infusion, the tumor is irradiated with epithermal neutrons. This leads to boron neutron capture reaction, which releases lethal doses of radiation within the cells containing BPA-F. BNCT has the ability to deliver high doses of radiation to the tumor with low toxicity to surrounding tissues. In the current study, BNCT toxicity and outcome were evaluated in a group of nine patients with persistent or recurrent LSCC after primary non-surgical treatment. Of the eight evaluable tumors, six (75%) responded to BNCT. No serious (Grade 4-5) toxicity was encountered. Despite good responses, only one patient was permanently cured without surgery. With treatment intensification, BNCT could show potential as a larynx-sparing treatment.
Originalspråkengelska
UtgivningsortHelsinki
Förlag
Tryckta ISBN978-951-51-3120-1
Elektroniska ISBN978-951-51-3121-8
StatusPublicerad - 2017
MoE-publikationstypG5 Doktorsavhandling (artikel)

Vetenskapsgrenar

  • 3125 Öron-, näs- och halssjukdomar, ögonsjukdomar
  • 3122 Cancersjukdomar

Citera det här

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title = "Laryngeal cancer recurrence : prognostic factors and management",
abstract = "Laryngeal cancer is one of the most common head and neck cancers. The treatment of laryngeal squamous cell carcinoma (LSCC) has evolved towards non-surgical treatment, namely radiotherapy and chemoradiotherapy. However, the treatment outcome of LSCC has not improved. LSCC recurs in up to 30{\%} of patients. The current knowledge on prognostic factors for recurrence is too limited to aid in treatment decisions. In this study, the treatment outcome and recurrences of 342 patients treated with curative intent for LSCC at the Finnish university hospitals during 2001-2005 were evaluated. The outcome of T1a glottic carcinomas was excellent; none of the patients died of LSCC. The results for T2 carcinomas was worse than expected; the 5-year disease-specific survival for glottic and supraglottic carcinomas in this group was 78{\%} and 54{\%}, respectively. The results for T3-4 carcinomas were comparable with those reported in the literature. Recurrence was observed in 22{\%} of patients and 91{\%} of the recurrences occured within 36 months of treatment. None of the patients with glottic T1a tumors had recurrence after 36 months, which questions the feasibility of routine 5-year follow-up for this patient group. WHO performance status >0, presence of neck metastases, and non-surgical primary treatment were significant independent predictors of recurrence. Local recurrence of glottic LSCC could be successfully salvaged. Regional or distant recurrence and any recurrence of supraglottic LSCC carried a poor prognosis. These results underline the importance of sufficiently aggressive primary treatment, particularly for supraglottic LSCC. Some LSCCs persist or recur after non-surgical treatment. Currently, there are no validated tools to identify these tumors. In this study, the expression of survivin, an inhibitor of apoptosis, Wrap53β, a protein associated with DNA double-strand break repair and telomere elongation, and p16INK4a, a surrogate marker for human papillomavirus infection, and their relation to treatment response and prognosis was investigated in LSCC tissue samples of 149 Finnish and Swedish T2-3N0M0 glottic LSCC patients treated with radiotherapy or chemoradiotherapy. Survivin showed no predictive or prognostic value. Cytoplasmic expression of Wrap53β was associated with reduced disease-free survival and overall survival. P16INK4a expression was rare in LSCC patients (7{\%}) and more common among patients under the age of 60. In this younger patient group, none of the patients with p16INK4a expression experienced tumor recurrence. Surgery is the only standard salvage option for patients with LSCC recurrence after non-surgical therapy. Other salvage options are being investigated, one of which is boron neutron capture therapy (BNCT). In BNCT, non-radioactive boron, B10, commonly in a compound of boronophenylalanine-fructose (BPA-F), is infused intravenously. This substance has a tendency to accumulate preferably in tumor cells. After infusion, the tumor is irradiated with epithermal neutrons. This leads to boron neutron capture reaction, which releases lethal doses of radiation within the cells containing BPA-F. BNCT has the ability to deliver high doses of radiation to the tumor with low toxicity to surrounding tissues. In the current study, BNCT toxicity and outcome were evaluated in a group of nine patients with persistent or recurrent LSCC after primary non-surgical treatment. Of the eight evaluable tumors, six (75{\%}) responded to BNCT. No serious (Grade 4-5) toxicity was encountered. Despite good responses, only one patient was permanently cured without surgery. With treatment intensification, BNCT could show potential as a larynx-sparing treatment.",
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author = "Aaro Haapaniemi",
note = "M1 - 79 s. + liitteet Volume: Proceeding volume:",
year = "2017",
language = "English",
isbn = "978-951-51-3120-1",
series = "Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis",
publisher = "University of Helsinki",
number = "29/2017",
address = "Finland",

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Laryngeal cancer recurrence : prognostic factors and management. / Haapaniemi, Aaro.

Helsinki : University of Helsinki, 2017. 79 s.

Forskningsoutput: AvhandlingDoktorsavhandlingSamling av artiklar

TY - THES

T1 - Laryngeal cancer recurrence : prognostic factors and management

AU - Haapaniemi, Aaro

N1 - M1 - 79 s. + liitteet Volume: Proceeding volume:

PY - 2017

Y1 - 2017

N2 - Laryngeal cancer is one of the most common head and neck cancers. The treatment of laryngeal squamous cell carcinoma (LSCC) has evolved towards non-surgical treatment, namely radiotherapy and chemoradiotherapy. However, the treatment outcome of LSCC has not improved. LSCC recurs in up to 30% of patients. The current knowledge on prognostic factors for recurrence is too limited to aid in treatment decisions. In this study, the treatment outcome and recurrences of 342 patients treated with curative intent for LSCC at the Finnish university hospitals during 2001-2005 were evaluated. The outcome of T1a glottic carcinomas was excellent; none of the patients died of LSCC. The results for T2 carcinomas was worse than expected; the 5-year disease-specific survival for glottic and supraglottic carcinomas in this group was 78% and 54%, respectively. The results for T3-4 carcinomas were comparable with those reported in the literature. Recurrence was observed in 22% of patients and 91% of the recurrences occured within 36 months of treatment. None of the patients with glottic T1a tumors had recurrence after 36 months, which questions the feasibility of routine 5-year follow-up for this patient group. WHO performance status >0, presence of neck metastases, and non-surgical primary treatment were significant independent predictors of recurrence. Local recurrence of glottic LSCC could be successfully salvaged. Regional or distant recurrence and any recurrence of supraglottic LSCC carried a poor prognosis. These results underline the importance of sufficiently aggressive primary treatment, particularly for supraglottic LSCC. Some LSCCs persist or recur after non-surgical treatment. Currently, there are no validated tools to identify these tumors. In this study, the expression of survivin, an inhibitor of apoptosis, Wrap53β, a protein associated with DNA double-strand break repair and telomere elongation, and p16INK4a, a surrogate marker for human papillomavirus infection, and their relation to treatment response and prognosis was investigated in LSCC tissue samples of 149 Finnish and Swedish T2-3N0M0 glottic LSCC patients treated with radiotherapy or chemoradiotherapy. Survivin showed no predictive or prognostic value. Cytoplasmic expression of Wrap53β was associated with reduced disease-free survival and overall survival. P16INK4a expression was rare in LSCC patients (7%) and more common among patients under the age of 60. In this younger patient group, none of the patients with p16INK4a expression experienced tumor recurrence. Surgery is the only standard salvage option for patients with LSCC recurrence after non-surgical therapy. Other salvage options are being investigated, one of which is boron neutron capture therapy (BNCT). In BNCT, non-radioactive boron, B10, commonly in a compound of boronophenylalanine-fructose (BPA-F), is infused intravenously. This substance has a tendency to accumulate preferably in tumor cells. After infusion, the tumor is irradiated with epithermal neutrons. This leads to boron neutron capture reaction, which releases lethal doses of radiation within the cells containing BPA-F. BNCT has the ability to deliver high doses of radiation to the tumor with low toxicity to surrounding tissues. In the current study, BNCT toxicity and outcome were evaluated in a group of nine patients with persistent or recurrent LSCC after primary non-surgical treatment. Of the eight evaluable tumors, six (75%) responded to BNCT. No serious (Grade 4-5) toxicity was encountered. Despite good responses, only one patient was permanently cured without surgery. With treatment intensification, BNCT could show potential as a larynx-sparing treatment.

AB - Laryngeal cancer is one of the most common head and neck cancers. The treatment of laryngeal squamous cell carcinoma (LSCC) has evolved towards non-surgical treatment, namely radiotherapy and chemoradiotherapy. However, the treatment outcome of LSCC has not improved. LSCC recurs in up to 30% of patients. The current knowledge on prognostic factors for recurrence is too limited to aid in treatment decisions. In this study, the treatment outcome and recurrences of 342 patients treated with curative intent for LSCC at the Finnish university hospitals during 2001-2005 were evaluated. The outcome of T1a glottic carcinomas was excellent; none of the patients died of LSCC. The results for T2 carcinomas was worse than expected; the 5-year disease-specific survival for glottic and supraglottic carcinomas in this group was 78% and 54%, respectively. The results for T3-4 carcinomas were comparable with those reported in the literature. Recurrence was observed in 22% of patients and 91% of the recurrences occured within 36 months of treatment. None of the patients with glottic T1a tumors had recurrence after 36 months, which questions the feasibility of routine 5-year follow-up for this patient group. WHO performance status >0, presence of neck metastases, and non-surgical primary treatment were significant independent predictors of recurrence. Local recurrence of glottic LSCC could be successfully salvaged. Regional or distant recurrence and any recurrence of supraglottic LSCC carried a poor prognosis. These results underline the importance of sufficiently aggressive primary treatment, particularly for supraglottic LSCC. Some LSCCs persist or recur after non-surgical treatment. Currently, there are no validated tools to identify these tumors. In this study, the expression of survivin, an inhibitor of apoptosis, Wrap53β, a protein associated with DNA double-strand break repair and telomere elongation, and p16INK4a, a surrogate marker for human papillomavirus infection, and their relation to treatment response and prognosis was investigated in LSCC tissue samples of 149 Finnish and Swedish T2-3N0M0 glottic LSCC patients treated with radiotherapy or chemoradiotherapy. Survivin showed no predictive or prognostic value. Cytoplasmic expression of Wrap53β was associated with reduced disease-free survival and overall survival. P16INK4a expression was rare in LSCC patients (7%) and more common among patients under the age of 60. In this younger patient group, none of the patients with p16INK4a expression experienced tumor recurrence. Surgery is the only standard salvage option for patients with LSCC recurrence after non-surgical therapy. Other salvage options are being investigated, one of which is boron neutron capture therapy (BNCT). In BNCT, non-radioactive boron, B10, commonly in a compound of boronophenylalanine-fructose (BPA-F), is infused intravenously. This substance has a tendency to accumulate preferably in tumor cells. After infusion, the tumor is irradiated with epithermal neutrons. This leads to boron neutron capture reaction, which releases lethal doses of radiation within the cells containing BPA-F. BNCT has the ability to deliver high doses of radiation to the tumor with low toxicity to surrounding tissues. In the current study, BNCT toxicity and outcome were evaluated in a group of nine patients with persistent or recurrent LSCC after primary non-surgical treatment. Of the eight evaluable tumors, six (75%) responded to BNCT. No serious (Grade 4-5) toxicity was encountered. Despite good responses, only one patient was permanently cured without surgery. With treatment intensification, BNCT could show potential as a larynx-sparing treatment.

KW - Biomarkers, Tumor

KW - +analysis

KW - Boron Neutron Capture Therapy

KW - Carcinoma, Squamous Cell

KW - +pathology

KW - +therapy

KW - Disease-Free Survival

KW - Disease Progression

KW - Laryngeal Neoplasms

KW - +mortality

KW - +radiotherapy

KW - Neoplasm Invasiveness

KW - Neoplasm Recurrence, Local

KW - Neoplasm Staging

KW - Organ Sparing Treatments

KW - +methods

KW - Prognosis

KW - Risk Factors

KW - Treatment Outcome

KW - 3125 Otorhinolaryngology, ophthalmology

KW - 3122 Cancers

M3 - Doctoral Thesis

SN - 978-951-51-3120-1

T3 - Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis

PB - University of Helsinki

CY - Helsinki

ER -

Haapaniemi A. Laryngeal cancer recurrence : prognostic factors and management. Helsinki: University of Helsinki, 2017. 79 s. (Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis; 29/2017).