Purpose: PREDIX HER2 is a randomized Phase II trial that compared neoadjuvant docetaxel, trastuzumab, and pertuzumab (THP) with trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Rates of pathologic complete response (pCR) did not differ between the two groups. Here, we present the survival outcomes from PREDIX HER2 and investigate metabolic response and tumor-infiltrating lymphocytes (TIL) as prognostic factors. Patients and Methods: In total, 202 patients with HER2-positive breast cancer were enrolled and 197 patients received six cycles of either THP or T-DM1. Secondary endpoints included event-free survival (EFS), recurrence-free survival (RFS), and overall survival (OS). Assessment with PET/CT was performed at baseline, after two and six treatment cycles. TILs were assessed manually at baseline biopsies, while image-based evaluation of TILs [digital TILs (DTIL)] was performed in digitized full-face sections. Results: After a median follow-up of 5.21 years, there was no difference between the two treatment groups in terms of EFS [HR = 1.26; 95% confidence interval (CI), 0.54–2.91], RFS (HR = 0.69; 95% CI, 0.24–1.93), or OS (HR = 0.52; 95% CI, 0.09–2.82). Higher SUVmax at cycle 2 (C2) predicted lower pCR (ORadj = 0.65; 95% CI, 0.48–0.87; P = 0.005) and worse EFS (HRadj = 1.27; 95% CI, 1.12–1.41; P < 0.001). Baseline TILs and DTILs provided additional prognostic information to clinical parameters and C2 SUVmax. Conclusions: Long-term outcomes following neoadjuvant T-DM1 were similar to neoadjuvant THP. SUVmax after two cycles of neoadjuvant therapy for HER2-positive breast cancer may be an independent predictor of both short- and long-term outcomes. Combined assessment with TILs may facilitate early selection of poor responders for alternative treatment strategies.

Background: Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early‐stage T1–T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN‐technique in advanced OSCC (T3–T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC.Materials and Methods: In total, 85 patients with T1–T4 OSCC diagnosed 2019–2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT–CT to include all SNs.Results: Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early‐stage disease. T3–T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1–T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3–T4 versus T1–T2 (p = 0.0398).Conclusion: SN‐assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.

Purpose: Patients with persistent or recurrent papillary and poorly differentiated thyroid cancer can be effectively treated with radioiodine, if the tumour tissue is iodine-avid. However, iodine-avidity status is often unknown at the time of initial radioiodine treatment, limiting any adaptive approach. This study aimed to clarify the relationship between pre-therapeutic iodine avidity in primary tumour tissue, initial lymph node metastases and iodine uptake in subsequent metastases. Methods: Iodine avidity was prospectively assessed pre-therapeutically in 35 patients by injection of tracer amounts of iodine-131 two days prior to surgery. Iodine concentrations in resected tissue samples were measured, enabling accurate and histologically verifiable iodine avidity data for both primary tumour and initial lymph node metastases. Iodine uptake in persistent metastatic disease was assessed by review of radiology, and treatment response was examined through journal studies. Results: Out of data from 35 patients, 10 had persistent disease at presentation or during follow-up (range 19–46 months). Four patients had non-avid persistent metastatic disease, all with low iodine avidity in their primary tumours and initial lymph node metastases. Patients with low pre-therapeutic iodine avidity did not appear to have greater risk of persistent disease. Conclusion: The results indicate a close link between pre-therapeutically measured iodine concentrations in primary tumours with iodine avidity of any subsequent metastases.

Background: Small intestinal bacterial overgrowth (SIBO) is suggested in irritable bowel syndrome (IBS). Our primary aim was to define a discriminating threshold for a positive lactulose hydrogen breath test (LHBT) in SIBO. As a secondary aim, IBS was subdivided into SIBO and non‐SIBO groups. Methods: LHBT performed in 206 subjects, 74 healthy subjects, 39 SIBO patients with intestinal lesions, 77 IBS patients, and 16 nonhydrogen producers. Using scintigraphy and LHBT, orocecal transit time was set to 80 min. Peak hydrogen levels were compared between the groups. Values are mean and 95% confidence interval. Results: Using an 80‐min orocecal cutoff time, LHBT in healthy subjects had peak values of 8 (6–9) ppm and SIBO 38 (31–45) ppm ( p < 0.0001). The diagnostic cutoff 20 ppm verified a sensitivity of 77% and specificity of 88% and positive and negative predictions of 77% and 88%. With the same cutoff for IBS, the mean peak value was 21 (16–26) ppm ( p < 0.0001 vs. healthy) with a sensitivity of 39% and a specificity of 78% and positive and negative predictions of 77% and 84%. Separating IBS at 20 ppm, the low‐hydrogen group had a peak value of 6 (5–7) ppm (ns vs. healthy), and the high‐hydrogen group had a peak of 44 (38–49) ppm ( p < 0.0001 vs. healthy). After antibiotics, IBS with low hydrogen remained unchanged, whereas those with high hydrogen were reduced to control ( p < 0.01). Conclusion: With cutoff at 20 ppm, LHBT differentiates SIBO in patients with early high breath hydrogen peaks, subdividing IBS into non‐SIBO and SIBO groups; the latter may benefit from antibiotic treatment.

In PREDIX LumB patients with estrogen receptor positive and human epidermal growth factor receptor negative (ER + /HER2-) breast cancer > 20 mm and/or with lymph node metastasis were randomized 1:1 to receive either paclitaxel weekly for 12 weeks followed by palbociclib and endocrine therapy for 12 weeks (arm A), or the reverse sequence (arm B). Primary endpoint is objective radiologic response at 12 weeks (ORR ₁₂ ), and key secondary endpoints are ORR ₂₄ , pathologic complete response, event-free survival, safety and correlative studies of tissue and circulating biomarkers. Whole exome sequencing and RNA sequencing were performed on baseline fresh frozen tissue samples. In total, 179 patients comprise the intention-to-treat population. There is no statistically significant difference between the two arms in ORR ₁₂ (59% vs 45%, p = 0.058). An exploratory gene expression analysis identified differentially expressed genes and gene sets between responders and non-responders at 12 weeks. A predictive signature, CDKPredX, comprising 31 genes related to proliferation, ER signaling and immune activity was developed to identify patients resistant to chemotherapy but responding to palbociclib plus endocrine therapy (p _interaction =0.03). The predictive signature was independently validated in the CORALLEEN trial (p _interaction =0.048). Clinicaltrials.gov identifier: NCT02603679

Cutaneous squamous cell cancer (cSCC) is the second most common form of skin cancer, characterized by abnormal, accelerated growth of squamous cells. When caught early, most cSCCs are curable. About 5 percent of the cSCC cases have advanced to such an extent, generally metastatic, that they are far more dangerous, with very poor prognosis and challenging to treat. All efforts to find biomarkers, in blood or in the tumor itself, for early identification of patients with a risk for metastasis have so far failed. The present study describes a novel method that enables the identification of lymphocyte markers in tumor-draining lymph nodes. Six patients with advanced cSCC were analyzed using a combination of a sentinel lymph node biopsy (SLNB) protocol, fine needle aspiration (FNA), and flow cytometry. Immunological results from the sentinel nodes were combined with corresponding data from peripheral blood and unfixed tumor tissues. The result demonstrates a striking difference between the subsets of T-cells from the three compartments. Our interpretation of this first pilot study is that the ability to follow specific immunological markers on lymphocytes in tumor-draining lymph nodes will enable the identification of novel prognostic biomarkers not detectable in material from blood and tumor tissues.