HOHMS

Origin

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. It has been validated (in part) by subsequent advances in research and clinical practice.

Traditional Lung Cancer Treatment Paradigms

Lung cancer was considered a very rare disease in the early part of the last century, and all malignant lung tumors were considered equivalent for treatment purposes.

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. 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. 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.

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. 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

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.

Specific Histomolecular Strata in NSCLC

Adenocarcinomas:

EGFR MutationsK-ras MutationsEML4-ALK Fusions and MutationsSignet ring cell

Squamous cell carcinomas:

Small cell, poorly differentiatedBasaloid

Large cell carcinomas:

UndifferentiatedLymphoepithelioma-likeRhabdoid phenotype

Other NSCLC's:

Clear cell variantsGiant 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