Table 3. Responses to antifungal therapy in patients with invasive mold disease.
| Outcome, response | Criteria |
|---|---|
| Success | |
| Complete response | Survival and resolution of all attributable symptoms and signs of disease; plus |
| Resolution of radiological lesion(s); persistence of only a scar or postoperative changes can be equated with a complete radiological response; plus | |
| Documented clearance of infected sites that are accessible to repeated sampling (e.g., mold disease involving the palate, sinuses, or cutaneous lesions) | |
| Partial response | Survival and improvement of attributable symptoms and signs of diseasea; plus |
| At least 25% reduction in diameter of radiological lesion (s); plus | |
| Documented clearance of infected sites that are accessible to repeated sampling (e.g., mold disease involving the palate, sinuses, or cutaneous lesions) | |
| In cases of radiological stabilization (defined as a 0%–25% reduction in the diameter of the lesion), resolution of all attributable symptoms and signs of fungal disease can be equated with a partial response | |
| In cases of radiological stabilization, biopsy of an infected site (e.g., lung biopsy) showing no evidence of hyphae and negative culture results can be equated with a partial response | |
| Failure | |
| Stable response | Survival and minor or no improvement in attributable symptoms and signs of disease; plus |
| Radiological stabilization (defined as a 0%–25% reduction in the diameter of the lesion); or | |
| Persistent isolation of mold or histological presence of invasive hyphae in infected sites | |
| Progression of disease | Worsening clinical symptoms or signs of disease; plus |
| New sites of disease or radiological worsening of preexisting lesions; or | |
| Persistent isolation of mold species from infected sites | |
| Death | Death during the prespecified period of evaluation regardless of attribution |
NOTE. The minimum period of observation is at least 6 weeks in trials of primary therapy, but assessment of outcome at week 12 or later should be included as a secondary end point. For trials of salvage therapy, consider evaluation of the primary end point at least 12 weeks after enrollment.
Clear evidence of a radiological response (reduction in diameter by at least 25% with no new sites of disease) should be given more weight than subjective, nonspecific, or difficult-to-quantify symptoms or signs of disease. Thus, in the scenario of fungal pneumonia, we suggest that radiological improvement with persistence of fever or cough should be scored as a partial response. Because radiological improvement often lags behind clinical improvement, especially if a short-term period of evaluation is employed (see Invasive Aspergillosis and Other Mold Diseases), we suggest that radiological stabilization and resolution of all attributable symptoms and signs of disease can also be equated with a partial response. See text for discussion of serum galactomannan index as a promising correlate of therapeutic outcome.