Narrative review of theoretical considerations regarding HITHOC between past and future

Hyppocrates constructed the medicines-surgery-energy triangle which includes all therapeutical modalities. Hyperthermic intraoperative chemotherapy (HITHOC) is a synergy-based single stage multimodality treatment encompassing the locoregional manifestation of the systemic malignant process. Pleural space, thermal effect, lavage/irrigation and chemotherapy represent the basic science ports of the network hub: HITHOC. The malignant transformation and process of the pleural surface (and underlying lung) challenges space management and tissue control. Thermotherapy without local chemotherapy is insufficient, similar to the normothermic local irrigation aligned with anticancer agents. The local administration of combined heat-transfer fluid and chemotherapy with or without subsequent surgical removal offers reasonable outcome in extensive primary pleural neoplasms (malignant mesothelioma), advanced (> Stage IIIA) NSCLC, functionally inoperable lung cancer and pleural carcinosis from extrathoracic malignancies. Measured by symptom-free survival and the quality of life, HITHOC in its present form, offers a modest yet fully substantiated solution. HITHOC in combination with the local application of targeted therapy and/or immunotherapy administered in the pleural space are currently under investigation. Additional development including new acting substances, their solvents and the means regarding surgical delivery and anesthesiology techniques are sign posts up ahead. Level 2 evidence are required in order to stepping up the recommendation levels, rewriting protocols and guidelines, in which HITHOC earns its revered position in the decision making process it deserves.