The combination of immune checkpoint inhibitors and definitive radiotherapy is investigated for the multimodal treatment of cisplatin non-eligible locally advanced head and neck cancers (HNC). In the case of recurrent and metastatic HNC, immunotherapy has shown benefit over the EXTREME protocol, being already considered the standard treatment. One of the biggest challenges of multimodal treatment is to establish the optimal therapy sequence so that the synergistic effect is maximal. Thus, superior results were obtained for the administration of anti-CTLA4 immunotherapy followed by hypofractionated radiotherapy, but the anti-PD-L1 therapy demonstrates the maximum potential of radio-sensitization of the tumor in case of concurrent administration. The synergistic effect of radiotherapy–immunotherapy (RT–IT) has been demonstrated in clinical practice, with an overall response rate of about 18% for HNC. Given the demonstrated potential of radiotherapy to activate the immune system through already known mechanisms, it is necessary to identify biomarkers that direct the “nonresponders” of immunotherapy towards a synergistic RT–IT stimulation strategy. Stimulation of the immune system by irradiation can convert “nonresponder” to “responder”. With the development of modern techniques, re-irradiation is becoming an increasingly common option for patients who have previously been treated with higher doses of radiation. In this context, radiotherapy in combination with immunotherapy, both in the advanced local stage and in recurrent/metastatic of HNC radiotherapy, could evolve from the “first level” of knowledge (i.e., ballistic precision, dose conformity and homogeneity) to “level two” of “biological dose painting” (in which the concept of tumor heterogeneity and radio-resistance supports the need for doses escalation based on biological criteria), and finally to the “third level“ ofthe new concept of “immunological dose painting”. The peculiarity of this concept is that the radiotherapy target volumes and tumoricidal dose can be completely reevaluated, taking into account the immune-modulatory effect of irradiation. In this case, the tumor target volume can include even the tumor microenvironment or a partial volume of the primary tumor or metastasis, not all the gross and microscopic disease. Tumoricidal biologically equivalent dose (BED) may be completely different from the currently estimated values, radiotherapy treating the tumor in this case indirectly by boosting the immune response. Thus, the clinical target volume (CTV) can be replaced with a new immunological-clinical target volume (ICTV) for patients who benefit from the RT–IT association (Image 1).

Locally advanced head and neck cancer is a unique challenge for cancer management in the Covid-19 situation. The negative consequences of delaying radio-chemotherapy treatment make it necessary to prioritize these patients, the continuation of radiotherapy being indicated even if SARS-CoV-2 infection is confirmed in the case of patients with moderate and mild symptoms. For an early scenario, the standard chemo-radiotherapy using simultaneous integrated boost (SIB) technique is the preferred option, because it reduces the overall treatment time. For a late scenario with limited resources, hypo-fractionated treatment, with possible omission of chemotherapy for elderly patients and for those who have comorbidities, is recommended. Concurrent chemotherapy is controversial for dose values >2.4 Gy per fraction. The implementation of hypo-fractionated regimens should be based on a careful assessment of dose-volume constraints for organs at risks (OARs), using recommendations from clinical trials or dose conversion based on the linear-quadratic (LQ) model. Induction chemotherapy is not considered the optimal solution in this situation because of the risk of immunosuppression even though in selected groups of patients TPF regimen may bring benefits. Although the MACH-NC meta-analysis of chemotherapy in head and neck cancers did not demonstrate the superiority of induction chemotherapy over concurrent chemoradiotherapy, an induction regimen could be considered for cases with an increased risk of metastasis even in the case of a possible Covid-19 pandemic scenario.

Tumor heterogeneity and the multitude of mechanisms involved in the progression of gastric adenocarcinomas (GACs) are reflected in the incidence and mortality rates, which continue to be a problem in oncological pathology. The way in which immune inflammatory elements intervene in the modeling of the tumor environment and influence gastric carcinogenesis is insufficiently known. The study investigated the intratumoral and peritumoral distribution and density of T- and B-lymphocytes and macrophages in 54 cases of GAC in relation to the histological prognostic parameters of the tumors. Discohesive, mixed and tubular adenocarcinomas presented the highest value of cluster of differentiation (CD)45RO reactions in the tumor compartments. In the case of GAC with associated histological aggressiveness parameters, we found higher values of CD20 and CD68 reactions at the intratumoral level, and of CD45RO peritumorally, which suggests different immune immunophenotypes not only in relation to the tumor type, grade and stage, but also to the two compartments. These observations may be useful for establishing criteria for approaching and interfering with immune mechanisms in gastric carcinogenesis, which may improve patient prognosis.

Background: Guidelines recommend the early integration of palliative care in advanced cancer; however, “earliness” remains heterogeneously defined, with no temporal consensus, and timing studies are vulnerable to immortal-time bias and do not model competing risks. Objective: To evaluate a pre-specified three-month threshold as a prognostic marker of cancer-specific survival (CSS) and as a potential auditable indicator of timely access to palliative care. Methods: A retrospective observational cohort study of 147 consecutive adults with advanced locoregional or metastatic cancer, admitted to a Romanian palliative care center (2018–2022; median follow-up 26 months), was conducted. The six-stratum analytical framework comprised multivariable Cox regression, Fine–Gray models, Grambsch–Therneau coefficients, Imai–Keele–Tingley mediation, restricted mean survival time (RMST) with inverse probability of censoring weighting, and validation through landmark and left-truncation analyses. Results: Fifty-nine patients (40.1%) were referred within the first three months. Referral within three months was independently associated with a reduced risk of cancer-specific death in locoregional disease (adjusted hazard ratio [HR], 0.49; 95% confidence interval, 0.28–0.86) and metastatic disease (HR, 0.58). Fine–Gray models confirmed the association (subdistribution HR 0.52). The RMST benefit was + 18.7 months (locoregional) and + 4.3 months (metastatic), persisting across landmark and truncation analyses. Conclusion: The three-month threshold is independently associated with significantly better CSS and is robust across six analytical approaches. As the design is observational, the findings remain associative and hypothesis-generating. Relevance for patients: The proportion of patients referred within the first three months can be computed from routine documentation and, subject to external validation, could serve as an auditable indicator of access to palliative care.

Dermatofibrosarcoma protuberans (DFSP) is a rare form of skin cancer characterized by local aggressiveness, typically affecting individuals in the young to middle-aged adult range. The authors of this article aimed to present the clinical picture, as well as the therapeutic approach to a patient undergoing oncological surveillance with DFSP, analyzing the therapeutic response rate based on data published in specialized journals. A 72-year-old man was admitted to the radiation oncology department, having a 75/58 mm tumoral mass on the right posterior cervical region. The patient underwent two radical tumor excision surgeries and interval skin grafting, leading to a negative prognosis for the patient, as the tumor reappeared aggressively in a short period, four months, more exactly. The study highlighted the importance of surgical intervention, such as wide local excision, in preventing recurrence and the major role of initiating timely adjuvant treatment, including radiotherapy. The previously performed studies suggest that radiotherapy can be beneficial following resection with negative margins, and it can serve as primary therapy for patients with inoperable or incompletely excised DFSP. In this case, the only therapeutic response was stopping the progression of the tumor growth and macroscopic changes of the tumor surface with areas of necrosis. This study also discusses the use of imatinib as the only left therapeutic option, due to the lack of radiotherapy response.