Efficacy of Enzyme-Targeting Chemo-Radiosensitization Therapy for Locally Advanced Tumors and Post-operative Residual Tumors

Surgery alone, more or less demolitive, is the treatment of choice of vulvar cancers. Cure rates are high for early cancers only, while locally advanced tumors with or without inguinal adenopathies and recurrences have a bad prognosis. The excellent results of concurrent chemo-radiotherapy of anal cancers suggested to adopt the same approach for locally advanced vulvar cancers. The shrinkage of the tumor allowed surgery, often less demolitive than usual, and the pathological examination demonstrated an overall complete response in 40% of cases. Survival has been improved through this multidisciplinary approach. Patients not suitable for surgery obtained important remissions and an improved quality of life. Clinical experience at the Istituto Tumori of Milano is presented.

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A comparison of clinical and laboratory data on neutron therapy for locally advanced tumors

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/0360-3016(87)90342-7 ◽

1987 ◽

Vol 13 (12) ◽

pp. 1783-1791 ◽

Cited By ~ 17

Author(s):

Mary Catterall ◽

R.D. Errington ◽

David K. Bewley

Keyword(s):

Locally Advanced ◽

Laboratory Data ◽

Neutron Therapy ◽

Locally Advanced Tumors ◽

Advanced Tumors

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Intraarterial high-dose cisplatinum (IAHDP) as a part of the treatment of relapsed or locally advanced tumors of the head and neck (H&N): A feasibility study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e16000 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e16000-e16000

Author(s):

Manuel Sureda Gonzalez ◽

Antonio Moreno ◽

Joseba Rebollo ◽

A. Brugarolas ◽

Rosa Cañon ◽

...

Keyword(s):

Therapeutic Option ◽

Locally Advanced ◽

Unknown Origin ◽

Response Duration ◽

Complete Response ◽

Primary Treatment ◽

High Dose ◽

Locally Advanced Tumors ◽

Adenocarcinoma Of Unknown Origin ◽

Advanced Tumors

e16000 Background: IAHDP has been employed as a part of the treatment of relapsed or locally advanced H&N tumors with controversial results (RADPLAT protocol). We hypothesize that patients (pts) with relapsed or locally advanced tumors in several locations can be treated with IAHDP, in order to achieve a response, to be followed by a consolidation with radiotherapy, surgery or both. Methods: Pts with relapsed or locally advanced tumors of the H&N were treated with IAHDP (150 mg/m2/wk), after an initial supraselective angiography performed with the goal of mapping adequately the arterial supply. Prevention of toxicity with hyperhydration and simultaneous and delayed thiosulfate was done according to the previous schema of the RADPLAT protocol. Results: From June 2007 to September 2011, 11 patients – 8 M/ 3F; age 37-77 y, median 56 y- were treated (10 H&N epidermoid carcinomas, 1 orbitary mts of adenocarcinoma of unknown origin). A total of 50 cycles were administered (2-9 per pt, median 4). In 4 pts IAHDP was part of the primary treatment; 7 pts were treated in relapse. Three pts were retreated after relapse, one of them two times. Five pts received radiotherapy simultaneously with IAHDP. Toxicity was generally mild and reversible. Mucositis g4 was observed in 3 cycles, facial edema requiring extra dexametasone in 7, pain during infusion in 9, nausea and vomiting in 3, lasting ipsilateral hypoacusia in 1, persistent trismus in 1. No significant alterations of renal function were observed. One pt progressed after the first cycle; 7 pts presented partial response (duration 1-6 m, median 2 m; 2 of them were converted to a complete response with surgery); 2 pts presented complete response with IAHDP simultaneous to radiotherapy. Four pts remained with no evidence of disease at 3+, 15+, 16+ and 38+ m respectively. Conclusions: IAHDP constitutes a feasible and promising therapeutic option for selected pts and a consolidation with surgery and/or radiotherapy after IAHDP is possible. Further development of this approach is warranted.

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Neoadjuvant denosumab treatment of locally advanced giant cell tumor of bone (GCTB).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.11026 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 11026-11026 ◽

Cited By ~ 2

Author(s):

Piotr Rutkowski ◽

Louie Gaston ◽

Aneta Borkowska ◽

Silvia Stacchiotti ◽

Giacomo Giulio Baldi ◽

...

Keyword(s):

Locally Advanced ◽

Progression Free Survival ◽

Axial Skeleton ◽

En Bloc Resection ◽

Preoperative Treatment ◽

En Bloc ◽

Intralesional Curettage ◽

Primary Tumors ◽

Locally Advanced Tumors ◽

Advanced Tumors

11026 Background: Retrospective study on locally advanced GCTB patients (pts) treated with neoadjuvant Denosumab (Db) outside clinical trials in 6 European reference centers. Methods: From 138 pts (median age 30yrs) with histologically confirmed advanced GCTB treated with Db(2011-2016), we included into analysis 87pts who underwent surgery after preoperative Db. All 87 patients had locally advanced tumors with extensive soft tissue involvement(54) or penetration to joint, not amenable to limb-sparing surgery/primary curettage or with high risk of recurrence. In 39/42(93%) cases diagnosis was confirmed by H3F3Agene mutation. Median follow-up time -22 months. Results: Primary tumor was located in lower limb(54%; n = 47) -mostly in tibia(25%) and femur(23%), upper limb(33%; n = 29), and pelvis/axial skeleton/ribs(13%; n = 11). 68(78%) patients had primary tumors, 19(22%) recurrent tumors after surgery (+/-radiotherapy). Median Db duration was 7months (range 1.5-35months), 17pts received also Db postoperatively. 39(45%) had wide en-bloc resection -WE (+17 implantation of prosthesis), 48(55%) cases had intralesional curettage -C, no extremity amputation. Pts who underwent prosthetic replacement had longer median preoperative Db therapy as compared to pts without prosthesis. All pts demonstrated a response to Db Progression after surgical treatment was observed in 15 pts -13 of them after intralesional curettage (13/48, 27%); 9 patients underwent D re-challenge -all responded. Two-year progression-free survival (PFS; from Db start) rate was 80%, 91% in WE group vs 73% in C group (p = 0.04), one-year PFS (from operation date) rate was 84%: 92% in WE and 79% in C group(p = 0.01). Treatment was well tolerated with only 1 grade 3 toxicity. Conclusions: Our study confirms that Db is active in a neoadjuvant setting with excellent efficacy and short-term tolerability. It implies that neoadjuvant therapy with Db is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following Db raises questions about the optimal duration of preoperative treatment and if Db is indicated postoperatively.

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CDK12 upregulation and adverse correlation with tumor-associated immune cell infiltrates in prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.181 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 181-181

Author(s):

Marie C. Hupe ◽

Anne Offermann ◽

Cleopatra Schreiber ◽

Axel Stuart Merseburger ◽

Sven Perner

Keyword(s):

Prostate Cancer ◽

T Cells ◽

Immune Cell ◽

Locally Advanced ◽

Survival Rates ◽

Distant Metastases ◽

Genetic Alterations ◽

Primary Tumors ◽

Locally Advanced Tumors ◽

Advanced Tumors

181 Background: Biallelic loss of CDK12 has recently been identified as a novel subtype of prostate cancer (PCa). CDK12 altered PCa associates with elevated neoantigen burden and thus may be suitable for checkpoint inhibition. Up to now, data about CDK12 refer to its genetic alterations in PCa while its characterization on protein level and its association with tumor infiltrating T-cells are lacking. Methods: Immunohistochemistry (IHC) for CDK12 was performed on a PCa cohort including 74 benigns, 391 primary tumors from 222 patients, 63 locally advanced tumors, 92 lymph node (LN) metastases, and 56 distant metastases. CDK12 was categorized into negative, weak, moderate and high expression. Density of tumor associated T-cells per tumor area was assessed by IHC for CD3 and graduated into negative (<1%), slight (1-5%), weak (5-10%), moderate (10-50%) and high (>50%). Results: CDK12 significantly increases during PCa progression showing highest levels in LN and distant metastases while benign samples harbor no or weak CDK12 expression (ANOVA p<0.001). Kaplan-Meier curve reveals 5-year-biochemical recurrence free survival rates of 89.5%, 69.1%, 59.1% and 20.0% for primary tumors expressing no, weak, moderate and high CDK12 (log-rank p=0.05). High CDK12 expression significantly associates with attenuated tumor associated T-cells (p=0.009) revealing CD3 negativity in 64.7% of CDK12 high expressing tumors. Intratumoral CDK12 and density of CD3 positive T-cells correlates adversely in particular in locally advanced tumors (p=0.007). Overall, tumor associated T-cells are significantly reduced in distant metastases compared to local PCa (p<0.001). Conclusions: Our study highlights the prognostic potential of CDK12 for PCa and its overexpression in advanced tumors. Of note, CDK12 overexpressing tumors can be designated as immunologic “cold” tumors which is in line with their more aggressive phenotype. Concordantly, distant metastases show attenuated tumor associated T-cells supporting the poor response to immunotherapy.

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