De fleste store studier som har undersøkt forekomsten av ny (primær) kreft i voksen alder hos dem som fikk kjemoterapi eller strålebehandling for en kreftform som barn, viser at denne forekomsten er skremmende høy. Forskerne er nå noenlunde istand til å skille fra hverandre de forskjellige årsaker til denne høye forekomsten. Kreft i barndommen er i seg selv en risikofaktor for ny kreft i voksen alder, enten barnekreften behandles eller ikke. Men hvis barnekreften behandles med strålebehandling eller kjemoterapi, kommer definitivt en ny risikofaktor inn i bildet som er forbundet med selve behandlingen. Strålebehandling og kjemoterapi innebærer en monumental svekkelse og delvis destruksjon av mange vev og funksjoner i kroppen, hvis konsekvenser man vil se i form av økt relatert morbiditet og mortalitet for hvert år som går etter behandlingen. Denne relaterte morbiditeten kan dukke opp 10, 20 eller 30 år senere.
Studiene nedenfor er et mer eller mindre tilfeldig utvalg av hva man kan finne i PubMed-databasen på 2-3 timer. Vi har her forkusert på langtidsvirkningene av kjemoterapi og strålebehandling for noen av de kreftformer der legene mener at konvensjonell kreftbehandling har vært spesielt vellykket.
Studier som inkluderer flere kreftformer i barndommen
Henderson et al. (2007): Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study.
“Radiation therapy has been shown to induce bone and soft tissue sarcomas (19–21). Previous studies (10, 22–29) have focused mainly on secondary bone sarcomas and have investigated radiation-related and other treatment-related risk factors. Results of these studies indicate that exposure to radiation and/or chemotherapy is associated with risk. The Late Effects Study Group, a multi-institution international consortium, analyzed data from 64 patients with secondary bone sarcoma and found an association between bone sarcoma and radiation dose (10). An expanded group of 91 patients with secondary bone sarcomas in this cohort was analyzed in another study (22), and results indicated that exposure to anthracycline chemotherapy was associated with increased risk. Similarly, the National Registry of Childhood Tumours in Britain used a case–control design to analyze 55 patients with bone cancer tumors among 3-year survivors of childhood cancer diagnosed between 1940 and 1983 (30). This study found that an increased risk of bone cancers was associated with increased dose of radiation or increased alkylator dose exposure. In a smaller British and French survivor cohort (25), among 32 patients with secondary osteosarcoma, risk of secondary osteosarcoma among survivors of childhood solid tumors was found to be linearly associated with the local dose of radiation and the concentration of alkylating agents received. In contrast, a nested case–control study (26) in Nordic countries of 31 childhood cancer survivors with secondary sarcomas (including both bone and connective tissue tumors) found that exposure to radiation was the only treatment associated with risk.
Our study is unique in that we could compare patients who developed secondary sarcomas with those who did not, that it includes the largest group of patients with secondary sarcomas described, and that it includes secondary sarcomas of all histologic subtypes. Our findings are consistent with the known association between secondary sarcoma occurrence and radiation exposure… We demonstrated that an increased risk of secondary sarcomas was associated with both radiation therapy and increasing doses of alkylators or anthracyclines.”
Gold et al. (2003): Second neoplasms after megavoltage radiation for pediatric tumors.
“Patients in the radiation-treated cohort experienced increased mortality, were at an increased risk of developing an SN [second neoplasms], and should undergo increased medical surveillance as adults. The cumulative probability of developing an SN has increased substantially at 30 years, largely due to an increase in follow-up time. In addition, the cumulative probability curve does not show evidence of plateau after increased duration of follow-up. Finally, the emergence of secondary breast carcinoma in the current study was not noted in the previous analysis.”
Le Vu et al. (1998): Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood.
“The risk of a osteosarcoma was found to be a linear function of the local dose of radiation (excess relative risk per gray 5 1.8), and was found to increase with the number of moles of electrophilic agents per square meter but not with other drugs. No interaction was noted between radiotherapy and chemotherapy. Bilateral retinoblastoma, Ewing’s sarcoma and soft tissue sarcoma were found to render patients susceptible to a higher risk of developing an osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance of patients who were treated during childhood for bilateral retinoblastoma, Ewing’s sarcoma, soft tissue sarcoma, as well as other first cancer treated with radiotherapy plus high doses of chemotherapy, without focusing exclusively on the radiation field.”
Hodgkin sykdom
Bhatia et al. (1996): Breast Cancer and Other Second Neoplasms after Childhood Hodgkin's Disease.
1380 personer som fikk kjemoterapi og/eller strålebehandling som barn for Hodgkins sykdom i perioden 1955-1986, ble fulgt opp som voksne. De hadde 18 ganger (1800 %) høyere forekomst av kreft enn normalbefolkningen, og kvinnene hadde 75 (7500 %) ganger høyere forekomst av brystkreft enn normalbefolkningen av kvinner.
Wilms tumor
Taylor et al. (2008): Second primary neoplasms in survivors of Wilms' tumour - A population-based cohort study from the British Childhood Cancer Survivor Study.
1441 personer som fikk kjemoterapi og/eller strålebehandling som barn for Wilms tumor i perioden 1940-1991, ble fulgt opp som voksne. Disse hadde betydelig høyere hyppighet av kreft som voksne enn normalbefolkningen, særlig på de kroppspartier som hadde blitt mye eksponert for strålebehandling.
non-Hodgkin-lymfom
Hemminki et al. (2008): Risk of Subsequent Solid Tumors After Non-Hodgkin's Lymphoma: Effect of Diagnostic Age and Time Since Diagnosis.
I en stor svensk undersøkelse så man nærmere på 28.131 personer som hadde fått behandling for non-Hodgkin-lymfom (en stor gruppe kreftsykdommer der kreften utgår fra lymfeknuter). ”CONCLUSION: These data indicate that age at treatment determines both the magnitude of the initial relative risk and the time-dependent modulation of the response. Therapy-related damage persists at least 30 years and its toll of solid tumors is largest 21 to 30 years after diagnosis.”
Akutt lymfatisk leukemi (ALL)
Tavernier et al. (2007): Secondary or concomitant neoplasms among adults diagnosed with acute lymphoblastic leukemia and treated according to the LALA-87 and LALA-94 trials.
“Therapy-related secondary neoplasms have been identified in patients receiving radiotherapy, chemotherapy, or combined modality therapy for a variety of primary neoplasms. In childhood ALL studies have documented a clear relationship between prior therapeutic irradiation and the occurrence of CNS tumors, sarcomas of bone, and thyroid cancers. [14][17][28-30]. Such occurrences did not emerge from our study.”
Pui et al. (2003): Extended Follow-up of Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.
“Our results suggest a new working definition of cure: 10 or more years of continuous complete remission, a standard that could be used to gauge the effectiveness of current and future treatment plans… Conclusions: Children with acute lymphoblastic leukemia who did not receive radiation therapy and who have attained 10 or more years of event-free survival can expect a normal long-term survival. Irradiation is associated with the development of second neoplasms, a slight excess in mortality, and an increased unemployment rate.”
Retinoblastom
Kleinerman et al. (2005): Risk of New Cancers After Radiotherapy in Long-Term Survivors of Retinoblastoma: An Extended Follow-Up.
“We detected an enhanced effect for the risk of osteosarcomas after radiation with chemotherapy compared to radiation alone, which is consistent with the previous findings of Tucker et al… Radiotherapy likely contributed to the significantly increased risks that we observed for cancers of the brain, nasal cavities, and eye and orbit… CONCLUSION: Hereditary Rb predisposes to a variety of new cancers over time, with radiotherapy further enhancing the risk of tumors arising in the radiation field.”
Wong et al. (1997): Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk.
“CONCLUSIONS: Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood.”
Testikkelkreft
Richiardi et al. (2007): Second malignancies among survivors of germ-cell testicular cancer: A pooled analysis between 13 cancer registries.
“In this large study of survivors of germ-cell testicular cancer, we observed a 65% excess risk of having a second cancer when compared to the general population. We found an increased incidence of some solid tumors, the risk of which increased with duration of follow-up. Incidence of myeloid leukaemia was increased among survivors of nonseminoma, and, particularly, among those treated since 1990… Incidence of nonlymphoid leukaemia was increased, in particular, among survivors of nonseminoma and among those diagnosed in the 1990s, with a median induction time of less than 5 years. There was no excess risk of lymphoid leukaemia, in contrast with the results of a previous study.[35] Our findings are consistent with a leukemogenic effect of chemotherapy regimes for testicular cancer, probably reinforced by the introduction of etoposide… The increased risks found for tumors of gastrointestinal tract, for pancreatic cancer and for tumors of the urinary tract are consistent with an effect of radiotherapy, and with results of previous studies… In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role.”
Travis et al. (2005): Second Cancers Among 40 576 Testicular Cancer Patients: Focus on Long-term Survivors.
“Statistically significantly increased risks of solid cancers were observed among patients treated with radiotherapy alone (RR = 2.0, 95% CI = 1.9 to 2.2), chemotherapy alone (RR = 1.8, 95% CI = 1.3 to 2.5), and both (RR = 2.9, 95% CI = 1.9 to 4.2).”
20-30 år etter behandling for brystkreft
Brown et al. (2007): Risk of second non-hematological malignancies among 376,825 breast cancer survivors.
“Although the absolute risks were small, we found persistent risks of second non-hematological malignancies excluding breast 30 or more years after breast cancer diagnosis, particularly for women diagnosed at young ages with localized disease.”
Galper et al. (2002): Second nonbreast malignancies after conservative surgery and radiation therapy for early-stage breast cancer.
“CONCLUSIONS: SNBMs [second nonbreast malignancies] occur in a substantial minority (8%) of patients treated with conservative surgery and radiotherapy. However, the absolute excess risk compared with the general population is very small (1%). This excess risk is only evident after 5 years. In particular, a slightly increased incidence of lung SNBMs and a somewhat larger increase in ovarian cancer among younger patients was found.”
Vil du se flere studier?
For flere studier anbefaler vi å besøke web-basen til The Childhood Cancer Survivor Study (CCSS). [Published research] [Abstracts].