Castration resistant prostate cancer (CRPC)

It is defined as medical or surgical castration, with castrate serum testosterone < 50 ng/dl, or < 1.7 nmol/l, plus one of the following types of progression [1]:

• Biochemical progression:
• Three consecutive rises in total prostate-specific antigen (PSA), at least 1 week apart, resulting in two 50% increases over the nadir, and at least one total PSA > 2 ng/ml [1];
• Or a rising total PSA that is greater than 2 ng/mL higher than the nadir, the rise has to be at least 25% over nadir and the rise has to be confirmed by a second total PSA at least three weeks later [2];
• For CRPC diagnosis, PSA progresses despite secondary hormonal manipulations, including anti‐androgen withdrawal for at least 4 weeks [3].
• Radiologic progression: The appearance of new lesions, either two or more new bone lesions on bone scan or a soft tissue lesion using the Response Evaluation Criteria in Solid Tumours (RECIST).

Bibliographic reference:

[1] Cornford P, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol. 2017 Apr;71(4):630-642. Available at: https://doi.org/10.1016/j.eururo.2016.08.002.

[2] Scher HI, Halabi S, Tannock I, et al.; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. Available at: https://doi.org/10.1200/jco.2007.12.4487.

[3] Heidenreich A, Aus G, Bolla M, et al.; European Association of Urology. EAU guidelines on prostate cancer. Eur Urol. 2008 Jan;53(1):68-80. Available at: https://doi.org/10.1016/j.eururo.2007.09.002.

Cutaneous areas at risk for non-melanoma skin cancer

The National Comprehensive Cancer Network (NCCN) guidelines (squamous cell carcinoma [1] and basal cell carcinoma [2]) classify high-risk lesions by size and location, as follows:

• 2 cm or more in diameter in low-risk locations (areas L):
• trunk and extremities, but not including the pretibia, hands, feet, ankles, and nail units.
• 1 cm or more in diameter in moderate-risk locations (area M):
• cheeks, forehead, scalp, neck, and pretibia.
• The area H, independent of size:
• The "mask area" of the face:
• Central face, eyelids, eyebrows, periorbital, nose, lips (cutaneous and vermillion), chin, mandible, preauricular and postauricular skin/sulci, temple, and ear.
• Genitalia, hands, and feet.

Head and neck H and M areas:

Source: [3]

Source: [4]

Body H, M, and L areas [3]:

Bibliographic references:

[1] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Squamous Cell Skin Cancer, Version 2.2020 - July 14, 2020 [Internet]. Nccn.org. 2020 [cited 12 October 2020]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf.

[2] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Basal Cell Skin Cancer, Version 1.2020 - October 24, 2020 [Internet]. Nccn.org. 2020 [cited 12 October 2020]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.

[3] Blechman et al. Application of Mohs micrographic surgery appropriate-use criteria to skin cancers at a university health system. J Am Acad Dermatol. 2014 Jul;71(1):29-35. Available at: https://doi.org/10.1016/j.jaad.2014.02.025.

[4] Dębski T, et al. Basal cell carcinoma. Current views (Part II). Diagnostics and treatment. Borgis - Postępy Nauk Medycznych 2009;9:706-13 [cited 12 October 2020]. Available at: http://ksiaznica.home.pl/pnm/spnm.php?ktory=518.

Castleman disease

It «is a rare disease of lymph nodes and related tissues. It was first described by Dr. Benjamin Castleman in the 1950s. It is also known as Castleman’s disease, giant lymph node hyperplasia, and angiofollicular lymph node hyperplasia (AFH). Castleman disease is not cancer. Instead, it is called a lymphoproliferative disorder. This means there is an abnormal overgrowth of cells of the lymph system that is similar in many ways to lymphomas (cancers of lymph nodes).

Even though Castleman disease is not officially cancer, one form of this disease (known as multicentric Castleman disease) acts very much like lymphoma. In fact, many people with this disease eventually develop lymphomas. And like lymphoma, Castleman disease is often treated with chemotherapy or radiation therapy.»

«Castleman disease is classified by how much of the body it affects. The main forms of Castleman disease are called localized and multicentric.»

«Infection with certain viruses plays a role in at least some cases of Castleman disease.

Multicentric Castleman disease is more common in people infected with HIV (human immunodeficiency virus), (...). Doctors sometimes group patients with multicentric Castleman disease into those who are infected with HIV (HIV positive) and those who are not infected (HIV negative).

In recent years, it’s become clear that another virus, known as human herpesvirus-8 (HHV-8) or Kaposi sarcoma herpesvirus (KSHV), is often found in the lymph node cells of people with multicentric Castleman disease. In fact, HHV-8 is found in the lymph nodes of nearly all Castleman disease patients who are HIV positive. Some doctors have suggested classifying Castleman disease based on whether the cells contain HHV-8.»

Bibliographic reference: The American Cancer Society medical and editorial content team, 2018. What Is Castleman Disease? [online] Cancer.org. Available at: <https://www.cancer.org/cancer/castleman-disease/about/what-is-castleman-disease.html> [Accessed 4 October 2020].

Charlson comorbidity index (CCI)

It predicts 10-year survival in patients with multiple comorbidities.

Online calculator.

Bibliographic reference: Charlson Comorbidity Index (CCI) - MDCalc [Internet]. Mdcalc.com. [cited 2019 Oct 13]. Available from: https://www.mdcalc.com/charlson-comorbidity-index-cci#use-cases.

Cancer-related survival

It is the time from diagnosis of cancer, or the start of treatment for cancer, to the date of death related to primary cancer.

Bibliographic reference: Wu YC, et al. Long-term results of pathological stage I non-small cell lung cancer: validation of using the number of totally removed lymph nodes as a staging control. Eur J Cardiothorac Surg. 2003 Dec;24(6):994-1001. Available at: https://doi.org/10.1016/S1010-7940(03)00567-0.

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy

CI: confidence interval; OS: overall survival; #: number of.

CI: confidence interval; PFS: progression-free survival.

Bibliographic reference: Hong JC, et al. Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis. PLoS One. 2018 Apr 12;13(4):e0195149. Available at: https://doi.org/10.1371/journal.pone.0195149.

Complete remission

«The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete response [1].» «Complete remission can also be described by some doctors as no evidence of disease (NED) [2]». «Remission may also refer to the disease-free period. Although remission is a word that can be used in relation to any cancer, it is most associated with leukemia and Hodgkin's disease and the other lymphomas [3].» «Remission is almost always the result of some form of cancer treatment, such as radiation or chemotherapy [not surgery], although there are documented cases in which cancer goes into remission on its own [4].»

Bibliographic references:

[1] NCI Dictionary of Cancer Terms. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/complete-remission. Accessed July 27, 2018.

[2] What Is Cancer Remission?. Mesothelioma + Asbestos Awareness Center. https://www.maacenter.org/blog/what-is-cancer-remission/. Accessed July 27, 2018.

[3] Sarg M, Gross A. The Cancer Dictionary. 3rd ed. New York: Facts on Fire; 2007:268.

[4] Cancer Remission Definition - Southeast Radiation Oncology Group, P.A. - SERO - Treat Cancer. Southeast Radiation Oncology Group, P.A. - SERO - Treat Cancer. https://treatcancer.com/blog/cancer-remission-definition/. Accessed July 27, 2018.

Carcinomatous meningitis

«Carcinomatous meningitis, also called meningeal carcinomatosis, neoplastic meningitis, or leptomeningeal carcinoma, is a form of metastatic cancer that has spread to the lining of the brain and spinal cord, the parts of the body that make up the central nervous system [1].» It «is a clinical syndrome caused by leptomeningeal metastases with widespread involvement of the cerebral cortex. The disease is associated with a poor prognosis [2].»

Source: Aboutcancercom. Available at: http://www.aboutcancer.com/meniingitis_1208_bmc.jpg. Accessed November 25, 2017.

Bibliographic reference:

[1] Carcinomatous Meningitis - Dictionary definition of Carcinomatous Meningitis | Encyclopedia.com: FREE online dictionary. Encyclopediacom. Available at: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/carcinomatous-meningitis. Accessed November 25, 2017.
[2] Kehrer JD, Stall B. 87 - Brain Metastases. In: Hristov B, Lin S, Christodouleas J. Radiation Oncology. 2nd ed. Philadelphia, USA: Wolters Klumer Health; 2015:568.

Circumferential resection margin

«The circumferential resection margin (CRM) is a term used in rectal carcinoma excision surgery. Pathologic evaluation of the resection margin on the excised rectum has been considered important for determining the risk of local recurrence. A margin of ≤1 mm is considered by some to be a negative prognostic factor for local recurrence (Park JS, et al., 2014, apud 1). (...). The CRM is not valid for excised colon covered by a peritoneal lining [1].» It is defined as the shortest distance from an affected region to the mesorectal fascia (MRF) and should be at least 1 mm [2]. It also called the radial margin. 

Bibliographic references:

[1] Weerakkody Y, Morgan M, et al. Circumferential resection margin | Radiology Reference Article | Radiopaedia.org. Radiopaediaorg. Available at: https://radiopaedia.org/articles/circumferential-resection-margin. Accessed November 17, 2017.
[2] Bond S, Joshi N, Petroudi S, Brady M. Estimating the mesorectal fascia in MRI. Inf Process Med Imaging. 2007;20:650-61. Available at: https://doi.org/10.1007/978-3-540-73273-0_54.

CTLA-4 (CD152)

The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or cluster of differentiation 152 (CD152), is a receptor on activated T cells that, functioning as an immune checkpoint, downregulates immune responses. It is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation. It acts as an off switch when bound to CD80 or CD86 on the surface of antigen-presenting cells [2]. It binds B7 molecules with a higher affinity than CD28, downregulating T-cell responses by inhibiting CD28 signaling [1].
CD80/CD86 are members of the immunoglobulin superfamily and present on mature antigen-presenting cells. They share their ligands (CD28 and CTLA-4) on T cells and play a major role as costimulatory molecules in the major histocompatibility complex class II-mediated peptide antigen presentation [1].
B7 molecules are a family of cell-surface proteins that function as costimulatory molecules transducing second signals for T cell-dependent immune responses [1].
CD28 is an activating receptor for B7 molecules present on naive T cells. The interaction of CD28 with B7 molecules provides the costimulatory or second signal for T-cell activation [1].
«(...) there is increasing interest in the possible therapeutic benefits of blocking CTLA-4 (using antagonistic antibodies against CTLA such as ipilimumab (FDA [Food and Drug Administration] approved for melanoma in 2011) as a means of inhibiting immune system tolerance to tumours and thereby providing a potentially useful immunotherapy strategy for patients with cancer» [2].

How does CTLA-4 prevent T-cell activation? Explore how tumor cells may use CTLA-4 to suppress the immune response:

Bibliographic references:

[1] Tortora, G., Bergmann, L., Lindh, M., Cervantes-Ruiperez, A., Dziadziuszko, R., Eckhardt, S., Lenz, H., Normanno, N., Perez, D., Scarpa, A., Syrigos, K., Tabernero, J. and Troiani, T. (2014). ESMO glossary in molecular biology of cancer. Viganello-Lugano, Switzerland: European Society for Medical Oncology.
[2] CTLA-4. Enwikipediaorg. 2017. Available at: https://en.wikipedia.org/wiki/CTLA-4. Accessed November 6, 2017.

Conformity index (CI)

It is defined as the ratio of the treated volume to the PTV (planning target volume) [1]. It is a tool for treatment plan analysis in conformal radiotherapy [2].

Bibliographic references:

[1] International Commission on Radiation Units and Measurements. ICRU Report 62. Prescribing, Recording and Reporting Photon Beam Therapy. Supplement to ICRU Report 50. Bethesda, MD: ICRU; 1999.

[2] Kataria T, Sharma K, Subramani V, et al. Homogeneity Index: An objective tool for assessment of conformal radiation treatments. J Med Phys. 2012 Oct;37(4):207-13. Available at https://doi.org/10.4103/0971-6203.103606.

Cytoreduction

It is the debulking, or reduction «(...) of the size of, a cancerous tumor. Surgery and radiation therapy are two common cytoreductive treatments used to debulk tumors. Debulking means to remove as much of the cancer as possible [1].» «(...) "cytoreduction" refers to reducing the number of tumor cells [2].» «Tumor debulking may increase the chance that chemotherapy or radiation therapy will kill all the tumor cells. It may also be done to relieve symptoms or help the patient live longer [3].» 

Bibliographic references:

[1] CancerCenter.com. (2017). Cytoreductive Therapy : Cancer Glossary | CTCA. [online] Available at: http://www.cancercenter.com/terms/cytoreductive-therapy/ [Accessed 15 May 2017].

[2] En.wikipedia.org. (2017). Debulking. [online] Available at: https://en.wikipedia.org/wiki/Debulking [Accessed 15 May 2017].

[3] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46635 [Accessed 15 May 2017].

Confidence interval (CI)

It is «a range of values, calculated from the sample observations, that is believed, with a particular probability, to contain the true parameter value» [1]. It is used «to express the degree of uncertainty associated with a sample statistic. A confidence interval is an interval estimate combined with a probability statement.» One «might describe the interval estimate as a "95% confidence interval". This means that if» one «used the same sampling method to select different samples and computed an interval estimate for each sample,» one «would expect the true population parameter to fall within the interval estimates 95% of the time» [2]. «Precision is taken to be the narrowness of the confidence interval. (...) The interval estimate is an expression of the uncertainty surrounding the point estimate and derives mainly from sampling variation as well as measurement variation/error. In general, the degree of uncertainty is inversely related to the size of the study. On one hand, if a study is too small, the uncertainty may increase to a level considered to be undesirable or useless. On the other, as the study size increases, the degree of uncertainty decreases, and the interval estimate becomes narrower» [3]. «Confidence intervals are preferred to point estimates and to interval estimates, because only confidence intervals indicate the precision of the estimate and the uncertainty of the estimate» [2].

Bibliographic references:

[1] Everitt, B. and Skrondal, A. (2010). The Cambridge dictionary of statistics. 4th ed. Cambridge, UK: Cambridge University Press.

[2] Stattrek.com. (2016). Statistics Dictionary. [online] Available at: http://stattrek.com/statistics/dictionary.aspx [Accessed 13 Nov. 2016].

[3] Broeck, J. and Brestoff, J. (2013). Epidemiology: Principles and Practical Guidelines. 1st ed. Dordrecht: Springer.

Choi-Baisi classification for bronchoscopic findings in esophageal cancer

This classification allows to identify bronchoscopic findings that predict resectability of esophageal carcinoma [1-3].

Category I: No abnormalities [2].

Category II: Impingement and no mucosal changes [2].

Category IIa: "(...) slight compression on the posterior wall of the trachea or left bronchus and no tumorous infiltration of the tracheobronchial tree; normal mobility of the tracheobronchial wall; and parallel and regular longitudinal folds of the pars membranacea. (...) This group of patients can be identified because the compression on the involved tracheobronchial tree is usually slight and its mobility is normal. (...) The tracheobronchial tree is only compressed and not infiltrated by the tumor, thus making a radical resection possible" [1].

Category IIb: "(...) compression in which the fixation of the tracheobronchial tree suggests tumorous invasion; impingement or deviation of the trachea or left bronchus or widening of the carina, with or without narrowing, associated with a reduction in mobility during breathing and coughing (ie, fixation of the involved tracheobronchial segment). The mucosa is still normal, but the longitudinal folds of the pars membranacea may be widened. (...) There is a frank infiltration of the tracheobronchial tree and a radical resection is unlikely. These patients can be downstaged by appropriate neoadjuvant" treatment "that would then make radical resection feasible" [1].

Category III: Mucosal invasion [2]/irregularities or tracheoesophageal fistula [3].

Bibliographic references:

[1] Baisi A, Bonavina L, Peracchia A. Bronchoscopic staging of squamous cell carcinoma of the upper thoracic esophagus. Arch Surg. 1999;134(2):140-143. Available at: http://dx.doi.org/10.1001/archsurg.134.2.140.

[2] Choi  TKSiu  FSLam  KWong  J Bronchoscopy and carcinoma of the esophagus, I: findings of bronchoscopy in carcinoma of the esophagus. Am J Surg. 1984;147(6):757-759. Available at: http://dx.doi.org/10.1016/0002-9610(84)90194-6.

[3] Choi  TKSiu  FSLam  KWong  J Bronchoscopy and carcinoma of the esophagus, II: carcinoma of the esophagus with tracheobronchial involvement. Am J Surg. 1984;147(6):760-762. Available at: http://dx.doi.org/10.1016/0002-9610(84)90195-8.

CTV (clinical target volume)

CTV includes the GTV as well as the regions of direct, local subclinical spread of disease that must be treated. The CTV often has a high tumor cell density nearest the GTV with decreasing density toward the periphery. The CTV volumes may not contain demonstrable tumor but are considered at risk, such as regional lymph nodes and their volumes, for subclinical spread.

Bibliographic reference:  Fisher, B. and Daugherty, L. (2013). C. In: L. Brady and T. Yaeger, ed., Encyclopedia of Radiation Oncology, 1st ed. Springer-Verlag Berlin Heidelberg, pp.77-154.