Complete Regression Of Disease Research Articles

Evaluating the Response of Hypofractionated Radiotherapy verses Conventional Radiotherapy with Concurrent Cisplatin in Advanced Fixed Node Head and Neck Carcinoma

Background: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumour sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). Objectives: To evaluate the efficacy of hypofractionated radiotherapy in advanced unresectable head neck cancer, in terms of response rate and evaluate the local and systemic toxicities of hypofractionated regimen with symptomatic improvement of radiotherapy and treatment compliance. Methods: A total of 50 cases of locally advanced head and neck cancer (stage cT4b and/or N3) without any evidence of distant metastasis were included in this study. These 50 cases were randomly distributed into study and control group containing 25 each. Radiotherapy consists of a single fraction of 6 Gy Per week for a total of 6 weeks. If the patient received less than 6weeks of treatment, he/she was excluded from study. Total dose given was 36 Gy in 6 fractions. All the patients were treated by unilateral or bilateral portal till 24 Gy and then off cord planning was done. Patients with complete disease regression after initially planned 36 Gy (BED-57.6Gy, considering alpha/beta of 10 and corresponding EQD2-48Gy) were offered further dose escalation depending upon tumour regression status, tolerability and toxicity according to institutional guidelines. Partial responders are given no treatment up to end of treatment period. Results: Among the study and control group, incidence of carcinoma of tonsil was 12% and 20%, carcinoma of base of tongue was 24% and 16%, carcinoma larynx 16% and 24%, respectively and Hematological toxicities (reference to blood hemoglobin level), Renal (reference to blood urea) were assessed according to WHO toxicity criteria in all cases weekly up to six weeks Among the study and control group, 8% and 12% had no acute hematologic reactions (χ2 = 0.22, p > 0.05), 56% and 48% had grade I hematologic reactions (χ2 = 0.32 p > 0.05,), 28% and 36% had grade II hematologic reactions (χ2 = 0.36, p > 0.05) and 8% and 4% had grade III hematologic reactions (χ2 = 0.35, p > 0.05) respectively. No patient had had grade IV hematological toxicity. Among the study and control group, 80% and76% had no acute renal toxicity. (χ2 = 0.11, p > 0.05), 20% and 24% had grade I hematologic reactions (χ2= 0.11 p > 0.05). No patients from either group develop grade II, III and IV renal toxicity. Conclusions: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted.

The Added Value of Steroid Injection Following Office-based Blue Laser Therapy of Benign Lesions of the Vocal Folds; Short-Term Effect in a Cohort of 43 Patients

To investigate the added value of steroid injection following office-based blue laser therapy of benign lesions of the vocal folds. Retrospective cohort analysis. The medical records and video-recordings of patients with benign lesions of the vocal folds who underwent office-based blue laser therapy in a tertiary referral center between February 2020 and October 2022 were reviewed. Patients were divided into two subgroups, those who underwent office-based blue laser therapy alone (n=23) and those who underwent office-based blue laser therapy with steroid injection (n=19). Disease regression and voice outcome measures included Voice Handicap Index-10 score, perceptual voice evaluation using the GRB grading, jitter, shimmer, noise to harmonic ratio, voice turbulence index, and maximum phonation time were reviewed. A total of 42 patients were included. The mean age was 54.7 ± 10.1 years. Lesions included polyps (n=21), Reinke's edema (n=19), and cysts (n=2). There was partial or complete disease regression in all patients who presented for follow-up (n=37). In patients who underwent blue laser therapy alone (n=19), 42.1% had complete regression and 57.9% had partial regression. In those who underwent blue laser therapy followed by steroid injection (n=18), 77.7% had complete disease regression and 22.3% had partial regression. The difference in disease regression between the two subgroups was statistically significant (P=0.027). The decrease in the mean Voice Handicap Index-10 score was also statistically significant with a higher mean being noted in the subgroup who underwent blue laser therapy followed by steroid injection (-10.5 ± 6.9 vs. -17.3 ± 11.8, P=0.031). There was no significant difference in the decrease in the perceptual evaluation scores nor in the decrease in jitter, shimmer, noise to harmonic ratio, and voice turbulence index between the two subgroups. There was also no significant increase in the maximum phonation time. Steroid injection after blue laser therapy improves disease regression and voice outcome of laser therapy.

Can we increase the cervical cancer screening interval with an HPV test for women living with HIV? Results of a cohort study from Maharashtra, India.

We are reporting (a) updated incidence of cervical intraepithelial neoplasia (CIN) among women who did not have colposcopic or histopathological disease at baseline and (b) disease outcomes among women treated for CIN and their follow-up HPV status; in a cohort of women living with HIV (WHIV). The median overall follow-up was 3.5 years (IQR 2.8-4.3). The incidence of any CIN and that of CIN 2 or worse disease was 16.7 and 7.0 per 1000 person-years of observation (PYO), respectively. Compared with women who were HPV negative at baseline, women who cleared HPV infection had 23.95 times increased risk of incident CIN 2 or worse lesions (95% CI 2.40-661.07). Women with persistent HPV infection had 138.18 times increased risk of CIN 2 or worse lesions (95% CI 20.30-3300.22). Complete disease regression was observed in 65.6% of the HPV positive women with high-grade CIN and were treated with thermal ablation but HPV persistence was seen in 44.8% of those with high-grade disease. Among those who did not have any disease at baseline and were also HPV negative, about 87% (95% CI 83.79-89.48) women remained HPV negative during consecutive HPV test/s with the median interval of 3.5 years. Long-term surveillance of WHIV treated for any CIN is necessary for the prevention of cervical cancer among them. Our study provides an early indication that the currently recommended screening interval of 3 to 5 years among WHIV may be extended to at least 5 years among HPV negative women. Increasing the screening interval can be cost saving and improve scalability among WHIV to support WHO's cervical cancer elimination initiative.

Abstract 5370: CARG-2020 a novel immunemodulatory approach to prevent recurrent ovarian cancer

Abstract Background: Immune therapy has been proven successful in multiple types of cancer, but not ovarian. Indeed, ovarian cancer is classified as a “cold tumor” with most tumors exhibiting low levels of T cell infiltrates and poor responses to immune checkpoint inhibitors. It is therefore important to develop better immune modulatory modalities that can improve clinical responses. In this study we evaluated the efficacy of CARG-2020, a virus-like vesicle (VLV) delivering three immune modulators (single chain IL-12, IL-17 antagonist and shRNA for PD-L1) in eliciting an effective and sustained anti-tumoral response to prevent recurrent disease in a syngeneic mouse model of ovarian cancer. Materials and Methods: Triple knockout (TKO; p53LSL-R172H/Dicerflox/flox/Ptenflox/flox) mouse ovarian cancer cells stably expressing the mCherry fluorescent protein were injected i.p. in C57BL/6 mice. Tumor growth was monitored by live imaging using mCherry fluorescence as surrogate for i.p. tumor burden. Treatment commenced when mCherry region of interest (ROI) area reached 20,000 photons/sec. Treatment groups were as follows (n=6/group): 1) PBS Control; 2) 1x10^6 PFU CARG-2020; 3) 1x10^6 PFU VLV-GFP (vector only control). All treatments were given i.p. for a total of 3 doses given 72h apart. Percentage of effector memory, central memory, and naïve CD8 T cells were measured by flow cytometry by staining for CD8, CD44, and CD62L. Results: Treatment with CARG-2020 induced a significant decrease in i.p. tumor burden compared to PBS Control (p=0.0044) and VLV-GFP (p=0.0011). Complete disease regression was observed in all CARG-2020-treated mice with a significant impact on overall survival conferring 100% protection (p=0.0008). Rechallenge of these animals with the same cancer cells failed to form tumors and analysis of splenocytes showed high levels of CD8+/CD44+/CD62- cytolytic effector memory T cells compared to tumor-bearing control and tumor-bearing VLV-GFP-treated mice (p=0.0011). Transfer of splenocytes from long term survivor mice into a new set of tumor-bearing, treatment-naïve mice, induced complete disease regression (p<0.0001, compared to PBS Control) and improved overall survival (p=0.0019, compared to PBS Control). Conclusion: We report the successful anti-tumoral effect of CARG-2020 by modulating the immune response in a syngeneic mouse model of recurrent ovarian cancer. CARG-2020, by enhancing the expression of IL-12 and blocking IL-17 and PD-L1, provided a long-term protection associated with the expansion of cytolytic effector memory CD8+T cells, which in addition to its antitumoral effect, provides protection against recurrent disease. Our results provide rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients. Citation Format: Ayesha B. Alvero, Alexandra Fox, Bhaskara Madina, Marie Krady, Timur O. Yarovinski, Valerian Nakaar, Bijan Almassian, Gil Mor. CARG-2020 a novel immunemodulatory approach to prevent recurrent ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5370.

A case of tuberculous dacryoadenitis with review of literature

Lacrimal gland inflammation is commonly due to viral infection, autoimmune, and idiopathic inflammatory disease. Orbital and adnexal tuberculosis (OTB) is a rare entity even in the TB endemic country of India. TB dacryoadenitis is one of the presentations in the OTB spectrum, with less than 25 cases in the literature. We report the case of a 14-year-old female primarily presented with unilateral dacryoadenitis and cold abscess at the lower lumbar region. Biopsy of lacrimal gland confirmed on histopathology as tuberculosis. Systemic investigation revealed pulmonary and extrapulmonary TB. She was treated with systemic category I anti-tubercular treatment resulting in complete regression of disease.

Eight-Day Methotrexate/Folinic Acid Regime as Single Agent Chemotherapy for Low-Risk Gestational Trophoblastic Neoplasia: A Retrospective Study

Objective: To evaluate the 8-day methotrexate (MTX)/folinic acid (FA) as a first-line chemotherapy regimen treatment in terms of complete regression of disease in women with low-risk gestational trophoblastic neoplasia (GTN). Material and Methods: All patients with low-risk GTN treated with an 8-day MTX/FA regimen were retrospectively included in the study. International Federation of Obstetrics and Gynecology and the modified World Health Organization Prognostic Scoring System were used to classify the risk of GTN. All women received diagnostic imaging evaluation before starting the treatment. The same MTX/FA regime was used repeating as a two-week cycle until normalization of the beta-human chorionic gonadotropin (ß-HCG), thus monthly ß-HCG follow-up was scheduled for up to 1 year. Results: Successful treatment was achieved in 56/66 (84.8%) patients. Nine (13.6%) women had resistance and 1 (1.6%) toxicity. The resistance patients were successfully treated with EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) protocol, whereas the patient who showed toxicity to the MTX/FA regime was successfully treated with actinomycin-D. Conclusion: Eight-day MTX/FA regime could be useful in low-risk GTN patients with good security margins. The toxicity rates in this protocol were determined as quite low. All resistance was treated successfully with the EMA-CO protocol.

PET imaging and treatment of pancreatic cancer peritoneal carcinomatosis after subcutaneous intratumoral administration of a novel oncolytic virus, CF33-hNIS-antiPDL1

Peritoneal carcinomatosis of gastrointestinal malignancies remains fatal. CF33-hNIS-antiPDL1, a chimeric orthopoxvirus expressing the human sodium iodide symporter (hNIS) and anti-human programmed death-ligand 1 antibody, has demonstrated robust preclinical activity against pancreatic adenocarcinoma (PDAC). We investigated the ability of CF33-hNIS-antiPDL1 to infect, help detect, and kill peritoneal tumors following intratumoral (i.t.) injection of subcutaneous (s.c.) tumors in vivo. Human PDAC AsPC-1-ffluc cells were inoculated in both the s.c. space and the peritoneal cavity of athymic mice. After successful tumor engraftment, s.c. tumors were injected with CF33-hNIS-antiPDL1 or PBS. We assessed the ability of CF33-hNIS-antiPDL1 to infect, replicate in, and allow the imaging of tumors at both sites (immunohistochemistry [IHC] and 124I-based positron emission tomography/computed tomography [PET/CT] imaging), tumor burden (bioluminescence imaging), and animal survival. IHC staining for hNIS confirmed expression in s.c. and peritoneal tumors following virus treatment. Compared to the controls, CF33-hNIS-antiPDL1-treated mice showed significantly decreased s.c. and peritoneal tumor burden and improved survival (p < 0.05). Notably, 2 of 8 mice showed complete regression of disease. PET/CT avidity for 124I uptake in s.c. and peritoneal tumors was visible starting at day 7 following the first i.t. dose of CF33-hNIS-antiPDL1. We show that CF33-hNIS-antiPDL1 can help detect and kill both s.c. and peritoneal tumors following s.c. i.t. treatment.

Aggressive Posterior Retinopathy of Prematurity (APROP): LASER as the Primary Modality of Treatment.

PurposeTo study the success rate of LASER as a primary modality of treatment in aggressive posterior retinopathy of prematurity (APROP) cases.MethodsThis is a prospective case series of 56 eyes of 28 preterm babies (males = 21) with APROP who underwent laser therapy. Babies were divided into groups on the basis of gestational age (GA), birth weight (BW), and postmenstrual age (PMA) at which treatment was performed. GA (in weeks): 28 (n = 7), 28–30 (n = 11), 30 (n = 10). BW (in grams): 1000 (n = 8), 1000–1200 (n = 10), 1200 (n = 10). PMA (in weeks): 32 (n = 6), 32–34 (n = 18), 34 (n = 4). Success was calculated as complete regression of disease without need for any other modality of treatment such as anti-vascular endothelial growth factor (anti-VEGF) or pars plana vitrectomy.Results The overall success rate was 94.64% (53/56). Two babies who needed additional modality of treatment were 28 weeks of GA (one eye) and 28–30 weeks (two eyes). One baby (one eye) was 1000 gm and the other (two eyes) was 1200 gm, while PMA at which additional treatment was needed was 30 weeks in one baby (one eye) and 33 weeks in the other (two eyes).Conclusion In this era of anti-VEGF treatment, even in cases of APROP, LASER should still be considered as a primary modality of treatment, as it is a one-time treatment without the concern of systemic side effects and recurrent/persistent avascular zones.

Outcomes of early versus deferred laser after intravitreal ranibizumab in aggressive posterior retinopathy of prematurity.

Purpose:The aim of this study was to report the treatment outcomes of early and deferred laser in infants of aggressive posterior retinopathy of prematurity (APROP) after initial treatment with intravitreal Ranibizumab (IVR).Methods:In a prospective, randomized, interventional study, infants with APROP received IVR (0.25 mg) and were randomized into two groups prior to laser. Laser was done at 1 week (group 1) or at 6 weeks or earlier if there was a recurrence of plus disease (group 2). The structural outcome, number of laser spots, duration of laser procedure and refractive error at 6 months were compared. Favorable structural outcome was defined as, complete regression of disease at 6 weeks after laser.Results:63 eyes of 32 infants with APROP were enrolled. Mean gestational age (GA) and birth weight (BW) were 30.2 ± 2.3 weeks and 1294 ± 372.8 grams respectively. GA, BW, and disease severity were comparable at baseline. 27 (90%) eyes in group 1 and 29 (93.5%) eyes in group 2 had favorable structural outcome (P = 0.61) at 6 weeks after laser. Eyes in group 2 (2149.8 ± 688.7) required lesser number of laser spots than group 1 (2570.8 ± 615) (P = 0.01). At six months, more eyes in group 1 had myopic refractive error (Mean spherical equivalent: –1.0D ± 1.3) than those in group 2 (Mean spherical equivalent: 0.5D ± 1.9) (P = 0.002).Conclusion:Infants with APROP receiving IVR have comparable structural outcomes after an early or deferred laser. Moreover, eyes undergoing deferred laser require less number of laser spots and have a less myopia at 6 months after laser.

Role of LASERS in stage 4A retinopathy of prematurity (ROP).

To study the anatomical success rate of light amplification by stimulated emission of radiation (LASERS) as first line of management in stage 4A retinopathy of prematurity (ROP). Observational, prospective case series of 14 eyes of 7 babies (males: 3, females: 4) with stage 4A ROP who underwent LASERS for stage 4A between January 2018 and July 2019. Gestation age (GA), birth weight (BW), and post-menstrual age (PMA) at which laser was done were noted in all cases. A number of clock hours of detachment at the time of presentation were noted in all babies. All babies were followed up up to 6 months after laser for any recurrence. Success was defined as complete regression of disease without the need of any other modality of treatment like anti-vascular endothelial growth factor (anti-VEGF) or pars plana vitrectomy. A total of 92.85% (13/14) showed complete regression of disease. One eye progressed to stage 4B ROP warranting lens-sparing vitrectomy (LSV). LASERS is an effective method of management without any need of anti-VEGF or surgical intervention even in babies with stage 4A ROP.

Acute Toxicity and Local Response using Three Fractions of High Dose Rate (HDR) Brachytherapy for Curative Treatment of Carcinoma Cervix.

Descriptive study. Radiation Oncology Section, Department of Oncology, The Aga Khan University Hospital, Karachi, Pakistan from January 2008 till December 2015. Protocol was formulated for carcinoma cervix to complete treatment in 7 weeks. Patients were treated with chemotherapy and pelvic EBRT to a total dose of 45 Gy/25 fractions, followed by three intracavitary HDR brachytherapy fractions of 8 Gy each. Vaginal toxicity and local clinical response was assessed at the end of treatment, at 4 and 8 weeks. A total of 57 patients were treated with HDR brachytherapy and 49 patients were evaluated for assessment of toxicity and response. According to FIGO staging system, two had stage IB2, one had IIA, thirty-six had IIB, seven had IIIB, one had IVA disease and two had IVB with para aortic nodes. Concurrent gemcitabine and cisplatin were given to 26 (46%); whereas, 28 (49%) received concurrent cisplatin alone. Grade III acute vaginal mucosal toxicity was seen in 52 and Grade IV acute vaginal mucosal toxicity was observed in 08 patients. At completion of treatment, 40 patients had complete clinical response, at 4 weeks follow-up, complete regression of disease was found in 3 more and at 8 weeks none had clinical residual disease. This regimen of HDR brachytherapy treatments is feasible, efficacious, and well-tolerated for carcinoma cervix in a setup with cost constraints. Long term toxicity and disease control remains to be reported with longer follow-up. Key Words: Carcinoma cervix, High dose rate brachytherapy, Acute toxicity, Local response, External beam radiation therapy, Intracavitary brachytherapy.

Abstract 5156: Targeting N-myristoylation in B-cell lymphomas as a therapeutic strategy

Abstract Myristoylation is the N-terminal modification of proteins with the fatty acid myristate. This process is mediated by two ubiquitously expressed N-myristoyltransferases, NMT1 and NMT2, and is critical for membrane targeting and cell signaling. Because NMT expression is increased in some cancers, we used three robotic screens to evaluate the potential of the potent pan-NMT inhibitor PCLX-001 on 300 cancer cell lines spanning the spectrum of human cancers. We discovered a marked increase in the sensitivity of hematological cancer cell lines, including B-cell lymphomas, to myristoylation inhibition. PCLX-001 consistently reduced both lymphoma cell proliferation and viability at concentrations lower than those needed to inhibit the growth of or to kill benign immortalized B cells. In lymphoma cell lines, PCLX-001 treatment inhibited early B-cell receptor (BCR) signaling events by disrupting membrane targeting of several myristoylated Src family kinases and promoted their ubiquitin-mediated degradation. Unexpectedly, PCLX-001 also promoted the degradation of non-myristoylated transcriptional activators P-ERK, c-Myc, NFκB and CREB downstream in the BCR signaling cascade, leading to loss of survival signals and apoptosis. Furthermore, compared to clinically approved drugs dasatinib and ibrutinib, PCLX-001 was more potent in vitro at inhibiting B-cell signaling, had a wider breadth of efficacy, and had greater selectivity thus sparing normal B cells. PCLX-001 treatment reduced tumor size in a time and concentration dependent manner in three B-cell lymphoma xenograft models and resulted in complete disease regression in two of these models, including an R-CHOP refractory lymphoma patient-derived xenograft. To investigate the potential mechanisms responsible for the sensitivity of hematological cancers to PCLX-001, we examined the NMT expression levels in cancer cells using publically available databases. Contrary to the reported NMT overexpression in some cancers, we found that hematological cancer cell lines and tumors both display significant reduction in NMT2 expression. The decreased NMT2 expression is significantly correlated with lower EC50 and poorer patient prognosis. Using the CRISPR-based genetic alteration Cancer Dependency Map, we discovered that cancer cells are highly dependent on functional NMT1, and that NMT1 dependency increases with low NMT2 expression. PCLX-001 treatment may mimic the effect of genetic alteration of NMT1 in hematological cancer cells low in NMT2 by pharmacologically inhibiting the remaining NMT1 in these cells. This results in an effect reminiscent of synthetic lethality since the vast majority of normal cells express both NMTs and PCLX-001 selectively kills NMT2-deficient cancer cells while sparing normal cells. Our findings support the ongoing development and eventual clinical trials of PCLX-001 as a therapy for hematological cancers. Citation Format: Erwan Beauchamp, Megan C. Yap, Maneka A. Perinpanayagam, Jay M. Gamma, Krista M. Vincent, Raymond Lai, Wei-Feng Dong, Manikandan Lakshmanan, Anandhkumar Raju, Vinay Tergaonkar, Soo Yong Tan, Soon Thye Lim, Lynne Postovit, Kevin D. Read, David W. Gray, Paul G. Wyatt, John R. Mackey, Luc G. Berthiaume. Targeting N-myristoylation in B-cell lymphomas as a therapeutic strategy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5156.

Application of Thulium Laser as Office-based Procedure in Patients With Vocal Fold Polyps

To report the voice outcome measures of thulium laser therapy as an office procedure in patients with vocal fold polyps. This is a retrospective chart review of all patients with vocal fold polyps who underwent office-based thulium laser treatment between November 2016 and December 2017. Demographic data were collected. Objective voice outcome measures included extent of resolution, type of closure, and mucosal wave characteristics. Also, subjective outcome measures were reported, namely, Voice Handicap Index-10. A total of 20 patients were enrolled with a mean age of 50.95 ± 14.70 years. All patients had unilateral vocal fold polyps except for one who had bilateral polyps. Out of the 20 patients, 16 had complete regression of disease and 4 had partial regression. The number of patients with incomplete glottal closure decreased from 12 pretreatment to only 1 patient posttreatment, and the number of patients with impaired mucosal waves decreased from 13 to 5. There was also a significant decrease in the mean VHI-10 score before and after treatment (15.61 vs. 4.61 P value < 0.001). Thulium laser can be used as an office procedure for the treatment of vocal fold polyps.

Клінічна ефективність місцевого застосування вагінальних супозиторіїв Протефлазід® у лікуванні цервікальної інтраепітеліальної неоплазії легкого та помірного ступенів, зумовленої вірусом папіломи людини

The objective: to study the effectiveness of topical vaginal suppositories Proteflazid® in the form of monotherapy for CIN-the I-II, caused by the human papilloma virus (HPV). Patients and methods. The study involved 50 women with cervical pathology caused by various strains of human papillomavirus (HPV). All the women were examined and treated in Vinnytsia city clinical hospital № 1. PAP test based on liquid-based cytology, determining proliferation markers HPV genotyping quantitative estimation, determination of the status of the vagina biocenosis bacterioscopy vaginal discharge performed in the laboratory Synevo. Results. Own clinical experience vaginal suppositories Proteflazid® as monotherapy for the treatment of cervical intraepithelial neoplasia mild to moderate from HPV infection, the complex evaluation of clinical efficacy based on the study of patients complaints, PAP-test based on liquid-based cytology, proliferation markers p16 and Ki- 67, viral load, colposcopy and results of histological examination of altered cervical sites showed a positive therapeutic effect with suppositories, which resulted in 96% of women achieved complete regression of disease, and 4% marked shift in the CIN-II CIN-I. Conclusion. The positive effect of the drug on the state of the vagina Proteflazid® microbiocenosis, good tolerability, ease of use and lack of side effects give reason for its use in the health care system. Key words: CIN-I-II, papillomavirus infection, suppositories Proteflazid®.

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy.

Validation of sentinel lymph node biopsy in breast cancer women N1–N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona

IntroductionThe aim of our study was to evaluate sentinel lymph node biopsy (SLNB) as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative SLNB patients. Material and methodsA multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1–T3, N1–N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing a SLNB followed by lymphadenectomy. ResultsA total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive SLNB (true positive), while 3 had a negative SLNB (false negative). Of the 28 true positive SLNB, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were SLNB negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. ConclusionsSLNB after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative SLNB.

Radiolabeled Polymeric Nanoconstructs Loaded with Docetaxel and Curcumin for Cancer Combinatorial Therapy and Nuclear Imaging

Growing evidence suggests that multifaceted diseases as cancer can be effectively tackled by hitting simultaneously different biological targets and monitoring patient‐specific responses. Combinatorial therapies, relying on the administration of two or more molecules with different cytotoxic mechanisms, are rapidly progressing in the clinic. Here, 100 nm spherical polymeric nanoconstructs (SPNs) are proposed for the combinatorial treatment of tumors by codelivering a potent antimitotic drug—docetaxel (DTXL)—and a broad spectrum anti‐inflammatory molecule—curcumin (CURC). In vitro, SPNs loaded with DTXL and CURC induce a threefold decrease in IC50 as compared to DTXL‐loaded SPNs. This synergic antitumor effect is also significant in mouse models of glioblastoma multiforme, where, after 22 d of treatment, the combinatorial approach leads to complete disease regression. At 90 d post‐treatment initiation, mice injected with DTXL + CURC SPNs have a 100% survival, whereas only 50% of the DTXL SPN treated mice survive. SPNs are also labeled with radioactive 64Cu(DOTA) molecules to document, via PET imaging, the progressive tumor mass shrinkage. Sensitization of DTXL by CURC is associated with NF‐κB downregulation and increased apoptosis. These theranostic nanoconstructs could be used for combinatorial treatment and assessment of therapeutic efficacy in other malignancies.

High Response Rates and Prolonged Survival in Patients With Corticotroph Pituitary Tumors and Refractory Cushing Disease From Capecitabine and Temozolomide (CAPTEM)

Rarely, corticotrophic pituitary tumors take on an aggressive form characterized by rapid growth, invasion into local structures, compression of cranial nerves, and possible spread to distant sites. When conventional surgery, radiation therapy, and hormones fail to control progression and symptoms, alternative therapies are needed. A novel chemotherapeutic regimen of capecitabine and temozolomide (CAPTEM), originally designed in our laboratory, demonstrated dramatic antineoplastic effects against corticotrophic pituitary tumors. We present a case series of 4 patients with aggressive, adrenocorticotrophic hormone--producing pituitary tumors who had previously depleted all surgical, radiation, and hormonal therapies and were then treated with CAPTEM. Dramatic clinical improvements in neurological deficits and Cushing symptoms were evident in all patients after treatment was initiated. Confirmed by radiographic imaging, 2 of 4 patients demonstrated complete regression of disease, 1 patient had a 75% regression, and the fourth patient has ongoing stable disease for > 4.5 years at the time of this writing. Immunohistochemical analysis of patients' tumor samples showed low O-methyguanyl methyltransferase expression and adequate levels of mismatch repair enzymes (MLH-1, MSH-2, MSH-6, and PMS-2), which are important for the in vivo efficacy of CAPTEM. This is the first report of prolonged antitumor response to and radiographic complete remissions as a result of CAPTEM in patients with aggressive pituitary tumors who had exhausted all other therapies.

Optos‐guided pattern scan laser (Pascal)‐targeted retinal photocoagulation in proliferative diabetic retinopathy

To investigate the clinical effects and safety of targeted pattern scan laser (Pascal) retinal photocoagulation (TRP) in proliferative diabetic retinopathy (PDR). Prospective and non-randomized study of 28 eyes with treatment-naive proliferative diabetic retinopathy (PDR). Single-session 20-ms-Pascal TRP strategy applied 1500 burns to zones of retinal capillary non-perfusion and intermediate retinal ischaemia guided by wide-field fluorescein angiography (Optos). Main outcome measures at 12 and 24 weeks included; PDR grade (assessed by two masked retina specialists); central retinal thickness (CRT); mean deviation (MD) using 24-2 Swedish interactive threshold algorithm (SITA)-standard visual fields (VF); and ETDRS visual acuity (VA). Following primary TRP, there was PDR regression in 76% of patients at 12 weeks (κ = 0.70; p < 0.001). No laser re-treatment was required at 4 weeks, and 10 eyes underwent repeat TRP at 12 weeks. Wide-field Optos angiography at 24 weeks showed complete disease regression in 37% and partial regression in 33%. Additional panretinal laser photocoagulation (PRP) was planned for active PDR in 30%. There were significant reductions in CRT over time (10.4 μm at 12-weeks, p = 0.007; 12.1 μm at 24-weeks, p = 0.0003). The MD on VFs improved after 12 weeks (+1.25 dB; p = 0.015) and 24 weeks (+1.26 dB, p = 0.01). The VA increased by +3 letters at 24 weeks (95% CI, 1.74-5.01; p < 0.0001). This pilot study reports that Optos-guided Pascal 20-ms TRP using 1500 burns for treatment-naive PDR is a promising procedure with favourable safety profile.

Pascal panretinal laser ablation and regression analysis in proliferative diabetic retinopathy: Manchester Pascal Study Report 4

To quantify the 20-ms Pattern Scan Laser (Pascal) panretinal laser photocoagulation (PRP) ablation dosage required for regression of proliferative diabetic retinopathy (PDR), and to explore factors related to long-term regression. We retrospectively studied a cohort of patients who participated in a randomised clinical trial, the Manchester Pascal Study. In all, 36 eyes of 22 patients were investigated over a follow-up period of 18 months. Primary outcome measures included visual acuity (VA) and complete PDR regression. Secondary outcomes included laser burn dosimetry, calculation of retinal PRP ablation areas, and effect of patient-related factors on disease regression. A PDR subgroup analysis was undertaken to assess all factors related to PDR regression according to disease severity. There were no significant changes in logMAR VA for any group over time. In total, 10 eyes (28%) regressed after a single PRP. Following top-up PRP treatment, regression rates varied according to severity: 75% for mild PDR (n=6), 67% for moderate PDR (n=14), and 43% in severe PDR (n=3). To achieve complete disease regression, mild PDR required a mean of 2187 PRP burns and 264 mm(2) ablation area, moderate PDR required 3998 PRP burns and area 456 mm(2), and severe PDR needed 6924 PRP laser burns (836 mm(2); P<0.05). Multiple 20-ms PRP treatments applied over time does not adversely affect visual outcomes, with favourable PDR regression rates and minimal laser burn expansion over 18 months. The average laser dosimetry and retinal ablation areas to achieve complete regression increased significantly with worsening PDR.