Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.
PurposeHybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-99mTc-nancolloid was evaluated in a large cohort of patients.Patients and methodsA prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR).ResultsA total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22–78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced.ConclusionWith ICG-99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4028-x) contains supplementary material, which is available to authorized users.
Photodynamic therapy (PDT) involves the use of a phototoxic drug which is activated by low powered laser light to destroy neoplastic cells. Multiple photosensitizers have been studied and tumors have been treated in a variety of head and neck sites over the last 30 years. PDT can effectively treat head and neck tumors, particularly those of the superficial spreading type, and the classic application of this technology has been in the patient with a wide field of dysplastic change and superficial carcinomatosis. Interstitial treatment has been used to treat more invasive cancer. Data is available from case series and institutional experiences, but very little randomized data is available. We review the mechanisms of action, historical development, available data, and current knowledge regarding PDT for the various head and neck subsites, and discuss possible future directions, with an emphasis on clinical application.
Opinion statementLocal residual disease occurs in 7-13 % after primary treatment for nasopharyngeal carcinoma (NPC). To prevent tumor progression and/or distant metastasis, treatment is indicated. Biopsy is the “gold standard” for diagnosing residual disease. Because late histological regression frequently is seen after primary treatment for NPC, biopsy should be performed when imaging or endoscopy is suspicious at 10 weeks. Different modalities can be used in the treatment of local residual disease. Interestingly, the treatment of residual disease has better outcomes than treatment of recurrent disease. For early-stage disease (rT1-2), treatment results and survival rates are very good and comparable to patients who had a complete response after the first treatment. Surgery (endoscopic or open), brachytherapy (interstitial or intracavitary), external or stereotactic beam radiotherapy, or photodynamic therapy all have very good and comparable response rates. Choice should depend on the extension of disease, feasibility of the treatment, and doctor’s and patient’s preferences and experience, as well as the risks of the adverse events. For the more extended tumors, choice of treatment is more difficult, because complete response rates are poorer and severe side effects are not uncommon. The results of external beam reirradiation and stereotactic radiotherapy are better than brachytherapy for T3-4 tumors. Photodynamic therapy resulted in good palliative responses in a few patients with extensive disease. Also, chemotherapeutics or the Epstein-Barr virus targeted therapies can be used when curative intent treatment is not feasible anymore. However, their advantage in isolated local failure has not been well described yet. Because residual disease often is a problem in countries with a high incidence of NPC and limited radiotherapeutic and surgical facilities, it should be understood that most of the above mentioned therapeutic modalities (radiotherapy and surgery) will not be readily available. More research with controlled, randomized trials are needed to find realistic treatment options for residual disease.
IntroductionNasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia.MethodsAll NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment.ResultsIn total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18–35) from day of diagnosis.ConclusionThe results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.
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