A coherent photon scanning tunneling microscope is presented. The setup employs heterodyne interferometry, allowing both the phase and the amplitude of the optical near field to be measured. Experimental results of measurements on a standing evanescent wave reveal the high resolution that is obtainable with such an approach. In fact we have measured the amplitude and the phase of the near field, with a resolution of 1.6 nm between sample points.

In this paper, we intend to gain an understanding of the interaction of light with microstructures. Measurements of amplitude and phase in the diffracted field close to gratings using a heterodyne scanning probe are presented. Coherent light diffracted by microstructures produces periodic features and can give birth to phase dislocations, also called phase singularities. Phase singularities are isolated points where the amplitude of the field is zero. We present measurements of such phase singularities with 10 nm spatial sampling and compare them with theoretical results obtained from rigorous diffraction calculations. The observed polarization effects reveal also important information about the vectorial field conversion by the fiber tip.

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Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up.Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases, and an activating mutation was detected in 33. Kaplan–Meier and Cox regression analyses were carried out to relate PFS and OS with different parameters.Results: Overall, we recorded a mean PFS and OS of 15.28 (95% CI: 10.36–20.20) and 24.6 (95% CI: 19.07–30.14) months, respectively, with 14 patients surviving free of progression for 10 years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in terms of PFS (hazard ratio (HR) = 0.58, p = 0.006) with a trend to a longer OS (HR = 0.69, P = 0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients, reporting a mean PFS and OS of 12.55 (95% CI: 7.19–17.9) and 20.28 (95% CI: 14.4–26.13) months, respectively. Immune-related adverse events (irAEs) were recorded in 24% of the cases and were related to a longer survival (HR = 0.36; P = 0.0001). Finally, patients' outcome was not correlated to sex, sidedness, and MT-K/N-ras.Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.

We will present experimental and theoretical studies of optical fields with subwavelength structures, in particular phase singularities and coherent detection methods with nanometric resolution. An electromagnetic field is characterized by an amplitude, a phase and a polarization state. Therefore, experimental studies require coherent detection methods, which allow one to measure the amplitude and phase of the optical field with subwavelength resolution. We will present two instruments, a heterodyne scanning probe microscope (heterodyne SNOM) and a high resolution interference microscope (HRIM). We will review some earlier work using the heterodyne SNOM, in particular the measurement of phase singularities produced by a 1 µm pitch grating with 10 nm spatial sampling. Using the HRIM we have investigated the intensity and phase distributions (with singularities) in the focal region of microlenses. The measurements are compared with the results calculated by rigorous diffraction theory.