Actuarial (versus actual)

«Its use is often extended (...) to include the Kaplan-Meier (KM) method, (...). Actual is a new term (...) to refer to a technique with several designations in the statistical literature, including cumulative incidence and crude, unadjusted, absolute, or observable probability [1].»

«Actuarial analysis, (...), is used to describe and compare survival probabilities by allowing for partial survival times (censoring). (...) The actuarial event-free (survival) curve for a nonfatal event, such as structural valve deterioration (SVD) of porcine valves, estimates the event-free probability for a population in which death has been eliminated. This overestimates the percentage of valves that will actually fail, because many patients die before the valve fails [2].»

«Unlike cumulative incidence [actual estimates], the KM attempts to predict what the latent failure probability would be if death were eliminated. To do this, the KM method assumes that the risk of dying and the risk of failure are independent. But this assumption is not true for many cardiac applications in which the risks of failure and death are negatively correlated (ie, patients with a higher risk of dying have a lower risk of failure, and patients with a lower risk of death have a higher risk of failure, which is a condition called informative censoring) [3].»

«When used for nonfatal events such as SVD, actual analysis estimates the percentage of patients who will have SVD (or the probability that an individual patient will experience SVD). The KM (actuarial) method attempts to estimate the percentage of SVD that would occur if patients never died. Also, KM depends on the assumption that death and SVD are independent, which they are probably not [1].»

Bibliographic references:

[1] Grunkemeier GL, Wu Y. Actual versus actuarial event-free percentages. Ann Thorac Surg. 2001 Sep;72(3):677-8. Available at: https://doi.org/10.1016/s0003-4975(01)03059-4.

[2] Grunkemeier GL, Jamieson WR, Miller DC, Starr A. Actuarial versus actual risk of porcine structural valve deterioration. J Thorac Cardiovasc Surg. 1994 Oct;108(4):709-18. PMID: 7934107. Available at: https://doi.org/10.1016/S0022-5223(94)70298-5.

[3] Grunkemeier GL, Jin R, Eijkemans MJ, Takkenberg JJ. Actual and actuarial probabilities of competing risks: apples and lemons. Ann Thorac Surg. 2007 May;83(5):1586-92. Available at: https://doi.org/10.1016/j.athoracsur.2006.11.044.

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QUANTEC (quantitative analysis of normal tissue effects in the clinic)

It summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic "Emami" paper [1,2].

Bibliographic references:

[1] Marks LB, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S10-9. Available at: https://doi.org/10.1016/j.ijrobp.2009.07.1754.

[2] Emami B, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. Available at: https://doi.org/10.1016/0360-3016(91)90171-y.

NTCP (normal tissue complication probability)

Rare cancers

The definition of rare tumors is not consensual. Rare cancers are defined as an incidence of fewer than 6 cases per 100.000 individuals per year (RARECARE workin group, Gatta et al. Eur J Cancer 2011).

According to DeSantis et al. ACS Atlanta. CA Cancer J Clin 2017, overall, approximately 20% of patients with cancer in the United States are diagnosed with a rare cancer. Based on the RARECARE workin group, Gatta et al. Eur J Cancer 2011, rare cancers are about 22% of all cancer diagnoses in Europe and 24% of the total cancer prevalence.

Rare cancers include > 300 histological subtypes and may affect all organs (Morfouace et al. EORTC, ESMO Open 2020). In addition, they can be grouped within 12 families of rare cancers (Casali et al. Fondazione IRCCS INT, Milan, ESMO Open 2020):

1. Epithelial tumours of head and neck:
• Larynx;
• Hypopharynx;
• Nasal cavity and sinuses;
• Nasopharynx;
• Major salivary glands and salivary gland type tumours;
• Oropharynx;
• Oral cavity and lip;
• Eye and adnexa;
• Middle ear.
2. Epithelial digestive tumours:
• Small intestine;
• Anal canal;
• Gallbladder and extrahepatic biliary duct.
3. Thoracic tumours:
• Epithelial tumours of the trachea;
• Thymomas and thymic carcinomas;
• Malignant mesothelioma.
4. Female genital tumours:
• Non-epithelial tumours of the ovary;
• Epithelial tumours of the vulva and vagina;
• Trophoblastic tumours of the placenta.
5. Male genital and urogenital tumours:
• Tumours of the testis and paratestis;
• Epithelial tumours of penis;
• Extragonadal germ cell tumours;
• Epithelial tumours of renal pelvis, ureter, and urethra.
6. Skin cancers and non-cutaneous melanoma:
• Mucosal melanoma;
• Uveal melanoma;
• Adnexal skin carcinomas;
• Kaposi sarcoma.
7. Sarcomas:
• Soft tissue sarcoma;
• Bone sarcoma;
• Gastrointestinal stromal tumours.
8. Neuroendocrine tumours:
• Gastrointestinal pancreatic;
• Lung;
• Other sites.
9. Endocrine organ tumours:
• Thyroid cancers;
• Parathyroid cancer;
• Adrenal cortex cancer;
• Pituitary gland cancer.
10. Central nervous system tumours:
• Glial tumours and others;
• Malignant meninioma;
• Embryonal tumours.
11. Paediatric tumours:
• Hepatoblastoma;
• Neuroblastoma and ganglioneuroblastoma;
• Nephroblastoma;
• Odontogenic malignant tumours;
• Olfactory neuroblastoma;
• Pancreatoblastoma;
• Pleuropulmonary blastoma;
• Retinoblastoma.
12. Haematological malignancies:
• Lymphoid malinancies;
• Myelodysplasctic syndromes;
• Myeloproliferative neoplasms (including mastocytosis);
• Myelodysplastic/myeloproliferative neoplasms;
• Myeloid/lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA (platelet derived growth factor receptor alpha), PDGFRB (platelet derived growth factor receptor beta), or FGFR1 (fibroblast growth factor receptor 1), or with PCM1-JAK2 (pericentriolar material 1-janus kinase 2);
• Acute myeloid leukaemia and related neoplasms.

Then, rare cancers are not so rare, and they are associated with multiple challenges including late and incorrect diagnosis, adverse outcomes, limited clinical expertise, weak evidence for best practice, and difficulties in collecting large series for research and in carrying out clinical trials (Boyd et al. BCCA, Vancouver, Lancet Oncol 2016).

Therefore, a global strategy is needed to join efforts to increase knowledge of this group of cancers.