Inhibition of Hyperprogressive Cancer Disease Induced by Immune-Checkpoint Blockade Upon Co-Treatment with Meta-Tyrosine and p38 Pathway Inhibitor.

Background Although immune-checkpoint inhibitors (ICI) are overall promissory for cancer treatment, they entail, in some cases, an undesired side-effect called hyperprogressive-cancer disease (HPD) associated with acceleration of tumor growth and shortened survival. Methods To understand the mechanisms of HPD we assayed the ICI therapy on two murine tumors widely different regarding immunogenicity and, subsequently, on models of local recurrences and metastases of these tumors. To potentiate the immune response (IR), we combined ICI with meta-tyrosine - that counteracts immune-suppressive signals - and a selective inhibitor of p38 pathway that proved to counteract the phenomenon of tumor-immunostimulation. Results ICI were therapeutically effective against both tumor models (proportionally to their immunogenicity) but only when they faced incipient tumors. In contrast, ICI produced acceleration of large and residual tumors. The combined treatment strongly inhibited the growth of large tumors and it managed to cure 80% of mice with local recurrences and 60% of mice bearing residual metastases. Conclusions Tumor enhancement was paradoxically correlated to a weak increase of the antitumor IR suggesting that a weak IR – different from a strong tumor-inhibitory one - may produce stimulation of tumor growth, mimicking the HPD observed in some clinical settings.

Spectrum of imaging manifestations of tumour recurrences in orthotopic neobladder

Continent diversion with orthotopic neobladder is the most upcoming form of urinary diversion postradical cystectomy. This allows patients to void through the native urethra preserving the maximal quality of life. These patients with greater life expectancies increasingly present with a wide range of late complications, which also include local recurrences involving neobladder. Such presentations on surveillance scans can be challenging for radiologists unfamiliar with expected post-surgical anatomy and usual sites of local recurrences. Tumour in neobladder, although rare, has predilection concerning specific sites of involvement and few distinct histological types. Major subtypes of such recurrences with corresponding radiological features on multimodality imaging have been discussed in this article. Management of such cases with revision of diversions is challenging, and surgeons expect a meticulous read of such scans before contemplating pelvic clearance and secondary diversions. This pictorial review aims to appraise the literature related to various primary and secondary types of tumours involving reservoir and anastomotic sites in an orthotopic neobladder, their relative incidences and illustrate salient imaging points with case examples.

Limited recurrence distance of glioblastoma under modern radiotherapy era

Background The optimal treatment volume for Glioblastoma multiforme (GBM) is still a subject of debate worldwide. The current study was aimed to determine the distances between recurring tumors and the edge of primary lesions, and thereby provide evidence for accurate target area delineation. Methods Between October 2007 and March 2019, 68 recurrent patients with GBM were included in our study. We measured the distance from the initial tumor to the recurrent lesion of GBM patients by expanding the initial gross tumor volume (GTV) to overlap the center of recurrent lesion, with the help of the Pinnacle Treatment Planning System. Results Recurrences were local in 47(69.1%) patients, distant in 12(17.7%) patients, and both in 9(13.2%) patients. Factors significantly influencing local recurrence were age (P = 0.049), sex (P = 0.049), and the size of peritumoral edema (P = 0.00). A total number of 91 recurrent tumors were analyzed. All local recurrences occurred within 2 cm and 94.8% (55/58) occurred within 1 cm of the original GTV based on T1 enhanced imaging. All local recurrences occurred within 1.5 cm and 98.3%(57/58) occurred within 0.5 cm of the original GTV based on T2-FLAIR imaging. 90.9% (30/33) and 81.8% (27/33) distant recurrences occurred >3 cm of T1 enhanced and T2-Flair primary tumor margins, respectively. Conclusions The 1 cm margin from T1 enhanced lesions and 0.5 cm margin from T2-Flair abnormal lesions could cover 94.8 and 98.3% local recurrences respectively, which deserves further prospective study as a limited but effective target area.

Outcomes of VAC temporization following the excision of microinvasive sarcomas pending negative formal pathologic margins.

e23559 Background: Microinvasive sarcomas can yield a high number of false negative intraoperative pathology margin analyses. Additional oncologic resection after soft tissue coverage is technically challenging and oncologically inaccurate. As a result the rate of local recurrence for these histologies can be 25% or higher. In select patients we have temporized the sarcoma tumor bed with a wound VAC pending final pathologic margins. If positive, the patient can return to the OR for a tumor bed excision. If negative, soft tissue coverage can proceed. Here we evaluate our outcomes using this approach. Methods: We retrospectively studied patients with primary sarcomas managed with a VAC temporizing approach from from 1/1/2003 to 12/1/2019 with a minimum of 2 years of oncologic follow-up. Patients with unplanned ("oopsie") excisions were also included. Our primary outcome was local recurrence. Data is presented as percentages or mean ± standard deviation where appropriate. Results: Sixty-three patients were included (Table). Mean age was 62.3 ± 22.3 (median 67.3) years, 23 (36.5%) were female, and mean age-adjusted charlson comorbidity index was 5.3 ± 1.9. Twenty-four (38.1%) had undergone “oopsie” excisions. R0 margins were achieved in 59 (93.7%) patients, while the other 4 were known R1 resections due to patient tolerance or anatomy. Five local recurrences (7.9%) were diagnosed 3.2 ± 1.5 years after surgery, of which 3 had known positive margins. Free flaps were needed in 17 (27.0%) patients. Metastatic disease was diagnosed in 8 (12.7%) patients, who all died of disease. Mean follow-up was 4.4 ± 2.9 years. Conclusions: VAC temporization results few local recurrences in patients with formally confirmed negative margins. This technique is particularly useful in the treatment of microinvasive disease or in the management of vulnerable hosts who may not be able to tolerate additional surgery in the future.[Table: see text]

The Clinical Significance of the Extent of Positive Surgical Margins in Partial Nephrectomy performed for Renal Cell Carcinoma

PurposeThis study aims to review the occurrences of extensive positive surgical margins and focal positive surgical margins after partial nephrectomy for kidney cancer, comparing their associations and clinical outcomes with those with negative surgical margins. Materials and MethodsBetween 2014 to 2019, a total of 137 partial nephrectomies for cancer was performed. Pathological surgical margins were classified according to negative surgical margins (n=156), extensive positive margins (n=7), or focal positive surgical margins (n=15). Peri-operative data, functional and oncological outcomes were compared among the three groups.ResultsBaseline clinical characteristics were comparable in all three groups except for gender, with a significantly greater proportion of male patients (P=0.02) with extensive positive surgical margins and focal positive surgical margins than negative surgical margins. Negative surgical margins was associated with shorter operative time compared with extensive and focal positive surgical margins. Pathologically, perinephric fat invasion was significantly associated (P<0.01) with positive surgical margins but there were no other differences in terms of cell type, grade and necrosis. There were a total of 4 local recurrences, all in the extensive positive surgical margins group with a median follow up period of 32.8 months.ConclusionsExtensive positive surgical margins and focal positive surgical margins share similar peri-operative associations when compared with negative surgical margins but have different pathological and oncological implications to each other. The higher association of pathological T3a stage with extensive positive margins may account for the finding that local recurrences exclusively occur in patients with extensive positive surgical margins.

Scrotal Verrucous Carcinoma: An Exceptional Localization of a Rare Tumor

Scrotal verrucous carcinoma is a rare entity. It is rarely metastatic especially in lymph nodes. Imaging is important for local extension in order to guide the surgical procedure. The diagnostic is histological. The treatment is based on surgical excision. The prognosis is relatively good, but local recurrences are frequent. We report a case of scrotal verrucous carcinoma in a 49-year-old man evolving for 1 year.