HOHMS
HOHMS (pronounced "Homes") is the medical acronym for "Higher-Order HistoMolecular Stratification", a term and concept which was first applied to lung cancer research and treatment theory.
The HOHMS Paradigm postulates that lung cancer cases can be more effectively treated if different tumors can be rationally classified into more homogeneous groups (or "strata"). These could then be used in randomized clinical trials with maximized potential for detecting significant differences in treatment regimens and other characteristics of the differing variants.
Rational stratification under the HOHMS paradigm uses a combination of histological criteria and molecular characteristics of the tumor.[1]
Origin[edit]
The HOHMS acronym was first applied to lung cancer and further developed in 2003 by Cliff Knickerbocker, Walton Distinguished Doctoral Fellow at the University of Arkansas. The HOHMS Paradigm is the major focus of Knickerbocker's doctoral dissertation.[2] It has been validated (in part) by subsequent advances in research and clinical practice.[1][3]
Traditional lung cancer treatment paradigms[edit]
Lung cancer was less common in the USA during the early part of the 20th century, before manufacturing of cigarettes by rolling machines. During this period, all malignant lung tumors were considered equivalent for treatment purposes.[4]
In the early 1960s, small cell lung carcinoma (SCLC) was recognized for its unique biological behavior, including a much higher frequency of widespread metastasis at diagnosis, and a higher frequency of sensitivity to chemotherapy and radiation therapy.[5] Early studies suggested that patients with SCLC fared better when treated with chemotherapy and/or radiation than when treated surgically, while non-small cell lung carcinoma (NSCLC) patients generally did better after surgery, and usually did not respond well to chemoradiation.[6][7] This "traditional" paradigm, wherein treatment options for lung cancer patients were based on histological stratification into two highly heterogeneous groups (i.e. SCLC vs. NSCLC), remained the standard for approximately 30–40 years.[8]
In the last two decades, however, the development of molecularly targeted agents have led to an increased emphasis on more precise typing and subtyping of lung carcinomas.[9] Although these new therapies have had little impact on the treatment of SCLC, some very promising results have been obtained in certain histiological types and subtypes of NSCLC's.
Rationale for the HOHMS paradigm[edit]
The "HOHMS Paradigm" posits that treatment regimens for lung cancer patients should be based on a high level of histological and molecular stratification to maximize response rates and survival prolongation, and minimize toxicity.
The choice of regimen should be based, insofar as is possible, on the results of large-scale randomized clinical trials. When large-scale trials have not been conducted, meta-analyses of databases of patient series and case reports can be utilized.
Histological stratification should be based on subtypes recognized in the 2004 revision of the World Health Organization (WHO) lung tumor typing system.[10][11]
Specific histomolecular strata in NSCLC[edit]
Adenocarcinomas:
- EGFR Mutations
- K-ras Mutations
- EML4-ALK Fusions and Mutations
- Signet ring cell
- Acinar
- Papillary
- Micropapillary
- Signet ring cell
Squamous cell carcinomas:
- Small cell, poorly differentiated
- Basaloid
Large cell carcinomas:
- Undifferentiated
- Lymphoepithelioma-like
- Rhabdoid phenotype
Other NSCLC's:
- Clear cell variants
- Giant cell carcinomas
HOHMS applied to certain lung cancer variants
- Undifferentiated large cell lung cancer has been shown to be particularly responsive to pemetrexed.
- EML4-ALK (+) lung cancers
- Acinar predominant adenocarcinoma and crizotinib
- Signet ring cell adenocarcinoma and crizotinib
- Papillary adenocarcinoma
- BAC with EGFR (+)
- Squamous cell carcinoma (cisplatinum/gemcitabine)
- Squamous cell carcinoma (no bevacizumab/anti-VEGF in cavitary or in near large vessels
References[edit]
- ^ a b Vincent MD (August 2009). "Optimizing the management of advanced non-small-cell lung cancer: a personal view". Curr Oncol. 16 (4): 9–21. doi:10.3747/co.v16i4.465. PMC 2722061. PMID 19672420.
- ^ Knickerbocker CL. The HOHMS Paradigm: Foundation of a new dynamic lung cancer classification system and treatment strategies. University of Arkansas: Unpublished doctoral dissertation.
- ^ Rossi G, Marchioni A, Sartori G, Longo L, Piccinini S, Cavazza A (2007). "Histotype in non-small cell lung cancer therapy and staging: The emerging role of an old and underrated factor". Curr Respir Med Rev. 3: 69–77. doi:10.2174/157339807779941820.
- ^ Watkin SW, Green JA (February 1990). "Small cell carcinoma of the bronchus: historical perspective of a treatable disease". J R Soc Med. 83 (2): 108–10. doi:10.1177/014107689008300217. PMC 1292509. PMID 2157005.
- ^ Watson WL, Berg JW (1962). "Oat cell lung cancer". Cancer. 15 (4): 759–68. doi:10.1002/1097-0142(196207/08)15:4<759::AID-CNCR2820150410>3.0.CO;2-6. PMID 14005321.
- ^ Lennox SC, Flavell G, Pollock DJ, Thompson VC, Wilkins JL (November 1968). "Results of resection for oat-cell carcinoma of the lung". Lancet. 2 (7575): 925–7. doi:10.1016/S0140-6736(68)91163-X. PMID 4176258.
- ^ Fox W, Scadding JG (July 1973). "Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus. Ten-year follow-up". Lancet. 2 (7820): 63–5. doi:10.1016/S0140-6736(73)93260-1. PMID 4123619.
- ^ Gazdar AF (October 2010). "Should we continue to use the term non-small-cell lung cancer?". Ann. Oncol. 21 (Suppl 7): vii225–9. doi:10.1093/annonc/mdq372. PMC 4542692. PMID 20943619.
- ^ Cooper WA, O'toole S, Boyer M, Horvath L, Mahar A (February 2011). "What's new in non-small cell lung cancer for pathologists: the importance of accurate subtyping, EGFR mutations and ALK rearrangements". Pathology. 43 (2): 103–15. doi:10.1097/PAT.0b013e328342629d. PMID 21233671.
- ^ Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad; et al., eds. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (PDF). World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 92-832-2418-3. Archived from the original (PDF) on 2009-08-23. Retrieved 2012-04-15.
- ^ D'Addario G, Früh M, Reck M, Baumann P, Klepetko W, Felip E (May 2010). "Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann. Oncol. 21 (Suppl 5): v116–9. doi:10.1093/annonc/mdq189. PMID 20555059.
External links[edit]
- Lung Cancer Home Page. The National Cancer Institute site containing further reading and resources about lung cancer.
- [1]. World Health Organization Histological Classification of Lung and Pleural Tumours. 4th Edition.