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Improved oncological treatment of anal cancer

Leon, Otilia LU (2019) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2019(23).
Abstract
Abstract
Background: Squamous cell cancer of the anus (SCCA) is a rare malignancy, but the incidence is increasing. It is
associated with humman papilloma virus infection. The standard treatment is radiotherapy (RT) combined with
chemotherapy, usually 5-fluorouracil (5FU)/Mitomycin C (MMC). This treatment is relatively effective, but
recurrence still represents a problem especially in locally advanced SCCA.
The overall aim of this thesis was to improve the treatment of SCCA by analysing a large Nordic population-based
cohort and to explore a new treatment strategy in a prospective phase I study, NOAC 8.
Methods: Studies I-III were based on a retrospective cohort comprising 1266 patients with SCCA... (More)
Abstract
Background: Squamous cell cancer of the anus (SCCA) is a rare malignancy, but the incidence is increasing. It is
associated with humman papilloma virus infection. The standard treatment is radiotherapy (RT) combined with
chemotherapy, usually 5-fluorouracil (5FU)/Mitomycin C (MMC). This treatment is relatively effective, but
recurrence still represents a problem especially in locally advanced SCCA.
The overall aim of this thesis was to improve the treatment of SCCA by analysing a large Nordic population-based
cohort and to explore a new treatment strategy in a prospective phase I study, NOAC 8.
Methods: Studies I-III were based on a retrospective cohort comprising 1266 patients with SCCA treated
according to Nordic guidelines between 2000 and 2007 (cohort 1), with definitive RT, alone or combined with
chemotherapy (CRT), stratified by tumor stage.The second cohort included 13 patients with locally advanced
SCCA enrolled in the NOAC 8 trial, investigating RT combined with cetuximab and 5FU/MMC, a combination that
had not been tested before. The primary aim was to determine the maximum tolerated dose (MTD) of
chemotherapy using a pre-defined dose escalation scheme.
Results: High age, male gender, large primary tumor, lymph node metastases, distant metastases, poor
performance status and non-inclusion into a protocol were all independent factors associated with worse
outcome.The treatment results were good, well in accordance with published randomized trials. A high incidence
(11%) of inguinal lymph nodes recurrence was observed in patients with small tumors where adjuvant lymph
irradiation was omitted. Surgery alone of early SCCA was associated with a high locoregional recurrence rate and
poor survival, which were significantly improved with postoperative RT/CRT.The outcome in patients with
metastatic SCCA was poor, but it was significantly better in patients receiving active treatment. Male gender,
metachronous disease and multiple metastatic sites were identified as prognostic factors associated with worse
prognosis.
The MTD of 5FU/MMC in combination with cetuximab and RT was determined.Dose limiting toxicity were
diarrhoea, febrile neutropenia and thrombocytopenia.
Conclusions: Good treatment results were obtained with widely implemented Nordic guidelines. We recommend
prophylactic inguinal lymph node irradiation also for small tumors. Postoperative RT/CRT is effective after primary
surgery for early SCCA. The addition of cetuximab to 5FU/MMC in combination with RT was a rather toxic
regimen but the side-effects were manageable.
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author
supervisor
opponent
  • Associate Professor Nilsson, Per J., Karolinska University Hospital
organization
alternative title
Optimering av analcancerbehandling
publishing date
type
Thesis
publication status
published
subject
keywords
Anal cancer, chemotherapy, Radiotherapy, Prognosis and survival, phase I/II trial, Cetuximab, metastatic
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2019
issue
23
pages
76 pages
publisher
Lund University: Faculty of Medicine
defense location
Onkologiklinikens föreläsningssal, Klinikgatan 5, Skånes Universitetssjukhus i Lund
defense date
2019-04-05 09:30:00
ISSN
1652-8220
ISBN
978-91-7619-752-3
language
English
LU publication?
yes
id
fb100283-a48a-4886-88c3-c5654d33b5a3
date added to LUP
2019-03-13 19:30:41
date last changed
2019-11-19 13:49:47
@phdthesis{fb100283-a48a-4886-88c3-c5654d33b5a3,
  abstract     = {Abstract<br/>Background: Squamous cell cancer of the anus (SCCA) is a rare malignancy, but the incidence is increasing. It is<br/>associated with humman papilloma virus infection. The standard treatment is radiotherapy (RT) combined with<br/>chemotherapy, usually 5-fluorouracil (5FU)/Mitomycin C (MMC). This treatment is relatively effective, but<br/>recurrence still represents a problem especially in locally advanced SCCA.<br/>The overall aim of this thesis was to improve the treatment of SCCA by analysing a large Nordic population-based<br/>cohort and to explore a new treatment strategy in a prospective phase I study, NOAC 8.<br/>Methods: Studies I-III were based on a retrospective cohort comprising 1266 patients with SCCA treated<br/>according to Nordic guidelines between 2000 and 2007 (cohort 1), with definitive RT, alone or combined with<br/>chemotherapy (CRT), stratified by tumor stage.The second cohort included 13 patients with locally advanced<br/>SCCA enrolled in the NOAC 8 trial, investigating RT combined with cetuximab and 5FU/MMC, a combination that<br/>had not been tested before. The primary aim was to determine the maximum tolerated dose (MTD) of<br/>chemotherapy using a pre-defined dose escalation scheme.<br/>Results: High age, male gender, large primary tumor, lymph node metastases, distant metastases, poor<br/>performance status and non-inclusion into a protocol were all independent factors associated with worse<br/>outcome.The treatment results were good, well in accordance with published randomized trials. A high incidence<br/>(11%) of inguinal lymph nodes recurrence was observed in patients with small tumors where adjuvant lymph<br/>irradiation was omitted. Surgery alone of early SCCA was associated with a high locoregional recurrence rate and<br/>poor survival, which were significantly improved with postoperative RT/CRT.The outcome in patients with<br/>metastatic SCCA was poor, but it was significantly better in patients receiving active treatment. Male gender,<br/>metachronous disease and multiple metastatic sites were identified as prognostic factors associated with worse<br/>prognosis.<br/>The MTD of 5FU/MMC in combination with cetuximab and RT was determined.Dose limiting toxicity were<br/>diarrhoea, febrile neutropenia and thrombocytopenia.<br/>Conclusions: Good treatment results were obtained with widely implemented Nordic guidelines. We recommend<br/>prophylactic inguinal lymph node irradiation also for small tumors. Postoperative RT/CRT is effective after primary<br/>surgery for early SCCA. The addition of cetuximab to 5FU/MMC in combination with RT was a rather toxic<br/>regimen but the side-effects were manageable.<br/>},
  author       = {Leon, Otilia},
  isbn         = {978-91-7619-752-3},
  issn         = {1652-8220},
  language     = {eng},
  number       = {23},
  publisher    = {Lund University: Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Improved oncological treatment of anal cancer},
  url          = {https://lup.lub.lu.se/search/ws/files/61679568/Improved_oncological_treatment_of_anal_cancer_Otilia_Leon.pdf},
  volume       = {2019},
  year         = {2019},
}