The primary objective of the present study was to assess the predictive value of iPET in HL treated with ABVD, the most widely used chemotherapy regimen for this disease.
Our study assessed the prognostic value of iPET in HL by requiring the use of the now standard Deauville criteria for interim analysis interpretation and that iPET is not used to modify treatment based on analysis result, which could potentially compromise the ability to assess its true predictive value. assess. To our knowledge, this study is the first of its kind in the Arab region and one of the few in non-Western developing countries.18.19.
The most important finding from our investigation is that iPET achieved after 2 or 4 cycles of ABVD is strongly correlated with EoT response, EFS and OS. In multivariate analyses, only iPET (P-value = 0.001) and disease stage (P-value = 0.008) remained independent predictors for EFS while iPET (P-value = 0.002), age (P-value = 0.001) and albumin (P-value = 0.048) retained their significance for OS. The independent prognostic value of iPET is consistent with previous reports in which iPET was found to be a strong predictor of an outcome above the well-established international prognostic score in advanced HL.seven. Similar results were reported by Hutchings et al. who found that iPET was a strong independent predictor of progression-free survival in HL above clinical stage and extranodal disease6.
The high negative predictive value (NPV) of iPET in HL of 91% using the 3 y-EFS endpoint in our study is consistent with what has been reported in the literature for early-stage HL and advanced.4,5,6,7,8,9,18,19,20. The high percentage of negative iPET exams (82% in our study) combined with the high NPV of iPET supports trials aimed at de-escalating ABVD therapy in an effort to reduce toxicity while maintaining efficacy10,11,12,13,14,15.
The PPV of iPET in our study based on 3-y-EFS was 59%, significantly lower than NPV. In fact, 21 of 44 patients (48%) with iPET-nCMR in our study converted to CMR at the end of treatment, with all remaining in CR until their last follow-up. The lower PPV of iPET found in our study is, in general, consistent with the results of previous studies, especially in early stage HL4,5,16. For example, a retrospective analysis of iPET-2 scans after 2 cycles of ABVD in an international cohort of 260 patients with advanced HL interpreted according to the Deauville criteria yielded a PPV of 73% compared to a NPV of 94 %4. Taken together, these data suggest that treatment escalation may not always be appropriate based on the iPET result alone and that confirmation of residual disease by biopsy may sometimes be necessary prior to treatment escalation. . This is reflected in the National Cancer Center Network (NCCN) clinical practice guidelines for the treatment of HL where biopsy is either mandatory or provided as an option for residual lesions with a Deauville score of 5 after 2 cycles of ABVD or other plans17. Indeed, a positive biopsy in this setting would warrant the administration of aggressive salvage chemotherapy which would otherwise be withheld if the biopsy is negative.21.
A limitation of the current study is that the majority of intermediate PETs were performed after 4 cycles of ABVD, whereas the majority of more recent studies have investigated PET after 2 cycles, with some guidelines recommending iPET-2 as the l optimal iPET.4,5,6,7,8,9,17,18,19,20. In this regard, it is important to note that our study found no association between the timing of iPET and iPET response status. Moreover, we did not find significant differences in the prognostic value of iPET-2 and i-PET-4, both showing highly significant differences in EFS between CMR and nCMR patients. Previous HL studies in which patients underwent both iPET-2 and i-PET-4 also failed to find significant differences in prognostic value between the two.6.
Nevertheless, it is important to note that iPET is now recommended after 2 rather than 4 cycles of ABVD17 probably because treatment modifications, if indicated, should occur as soon as possible after response is assessed6.
It should also be noted that today, patients with HL receive personalized treatment based on extensive data supporting the use of iPET to guide treatment and change management.10,11,13,14,15,16,17. However, iPET-based personalized treatment has only been recommended as a standard of care in recent years, for example in the 2020 NCCN Clinical Practice Guidelines17. Our study includes patients treated between 12/2013 and 12/2017 before personalized treatment was fully established as a new paradigm. Our data support the use of personalized treatment in the Jordanian/Arab population and this treatment is now offered to all patients with HL at our center.
An example of the use of i-PET for response-tailored therapy is the RATHL trial conducted in the UK in 1214 patients with advanced HLten. In this trial, patients with negative i-PET (defined as D5PS scores of 1 to 3) after 2 cycles of ABVD were randomized to continue with 4 additional cycles of treatment with the standard ABVD regimen or with bleomycin (a drug known to cause pulmonary toxicity) omitted, for a total of 6 cycles. There was no significant difference in PFS at 3 years between patients who received ABVD and those who received doxorubicin, vinblastine and dacarbazine (relative risk; 1.13; P-value = 0.35). Patients who received the 3-drug regimen had less infection, neutropenic fever, and lung toxicity. Thus, a negative iPET-2 can be used to spare patients cycle 3-6 bleomycin with maintained therapeutic efficacy and reduced toxicity.