Rational Patient Selection: Hope for Head & Neck Cancer and Beyond
In many disciplines, medical oncology included, change is slow.
The management of advanced cancer has progressed little over recent decades; as patients continue to receive standardized protocols” forcing each round peg into a square hole of treatment regardless of individual biology.
While many institutions pursue molecular profiles for insights into patient selection, these approaches have continued to fail, witnessed most recently by the SHIVA Study that provided no difference in outcome for DNA (genomic) selected patients over those who received “physician choice” (including some “physician's choice” being to not administer any therapy at all!).
Sometimes changes in medicine can be effected through the application of new concepts in more isolated environs leading to their subsequent adoption by the mainstream. While Hollywood glitterati jump aboard the more glamorous diseases in support of their favorite cause, unsung cancers that are every bit as lethal may now be leading the way toward acceptance of individualized therapy. Cancer of Head and Neck with an incidence of 59,000 per year may afford just such an opportunity. The biology of head and neck cancer has changed as Human Papilloma Virus (HPV) has become the predominant causative factor. HPV (+) patients tend to develop cancer in the tonsils or base of the tongue cancer and often occur in younger men. What is most interesting is that the HPV (+) patients tend to do better. Into this field have come very interesting new concepts, “patient selection” leading to “dose de-escalation”. Over recent years investigators have examined the possibility of using less not more treatment to achieve cures in patients with locally advanced head and neck cancers. The Eastern Cooperative Group (ECOG) 1308 guided treatment based upon clinical response (drug sensitivity) to initial chemotherapy. Those patients who showed complete clinical response to induction chemotherapy (whose tumors had disappeared) were given low dose radiation combined with the antibody Cetuximab. As the patients received a shorter course and lower dose of radiation, they had much lower toxicity. The most gratifying aspect of this study is that the patients who received the lower dose, de-escalated schedules, did the best. Thus patient selection based on drug sensitivity, with appropriate adjustments in dose and schedule led to superior outcomes. This has broad implications for all forms of cancer. Intelligent patient selection and dose schedules guided by drug responsiveness (individualized care) offer a very real hope for those patients confronting the random administration of toxic drug combinations with names like FOLFIRINOX and R-EPOCH. While the ECOG 1308 used “in vivo chemosensitivity” (that is measured in the patient’s body) the same determinations can be conducted outside the body using Ex Vivo Analysis (EVA-PCD). As this approach has already been shown to provide a 2-fold improvement in response (p < 0.0015) and 1.4 fold improvement in one year survival (p<0.02) one can only wonder why more oncologists aren’t taking advantage of this approach. Perhaps more patients should be asking their oncologists that same question.