Complete Radiological Remission Research Articles

Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Abstract PO5-18-10: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 48 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2024 -Primary outcome analysis: Q1/2027 Current accrual: In June 2023, 255 patients were recruited; the majority of them in Germany. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy). Citation Format: Toralf Reimer, Bernd Gerber, Thorsten Kuehn, Nikola Bangemann, Anke Kleine-Tebbe, Andrea Stefek, Ulrike Doerste, Carolin Hammerle, Oliver Hoffmann, Alexander Hein, Isabel Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-10.

Alternating chemotherapy with VDC-IE as effective first-line treatment in a patient with SMARCA4-deficient undifferentiated tumor

SummarySMARCA4-deficient undifferentiated tumor (SMARCA4-UTs) is an extremely rare and aggressive entity where no consensus on systemic treatment exists to date. We report the case of a 43-year-old woman with thoracic SMARCA4-UT who presented with rapid progression of disease after surgical resection and achieved complete radiologic remission under VDC-IE chemotherapy (vincristine, doxorubicin, and cyclophosphamide [VDC], alternating with ifosfamide and etoposide [IE]). The detailed case report is followed by a brief discussion and overview of current literature.

PET/CT with <sup>18</sup>F-FDG for TENIS Syndrome in a Patient with Bone Metastasis of Hurthle Cell Thyroid Cancer: a Clinical Case Report

A significant role in improving the prognosis of differentiated thyroid cancer (DTC) in the presence of bone metastases is determined by early diagnosis of metastases, timely and correctly selected treatment tactics for the patient. During dynamic follow-up of patients with DTC after combined treatment (thyroidectomy with radioiodine therapy) are determination of the level of oncomarkers (serum thyroglobulin and antibodies to thyroglobulin) and ultrasound diagnostic of the neck, scanning with radioactive iodine (if clinically indicated). In some cases, patients have TENIS-syndrome (Thyroglobulin Elevated Negative Iodine Scintigraphy, hereinafter TENIS-syndrome), characterized by high serum thyroglobulin level in blood and absence of radioactive iodine accumulation on post therapeutic scintigraphy. According to the research studies, PET/CT with 18F-FDG has high sensitivity and specificity (89 % and 72 %, respectively) in visualization of metastatic radioiodine refractory foci in TENIS-syndrome.This article presents a clinical case of a patient, a 52-year-old woman with Gurtle cell thyroid cancer (pT3aN0M0, stage I) with established TENIS syndrome. Thyroidectomy was performed in September 2019 and radioiodine therapy was performed in January 2022 due to suspected disease progression given high thyroglobulin levels. Given the absence of pathologic accumulation of 131I according to post-therapy radioiodine scanning, PET/CT with 18F-FDG was performed, which revealed a solitary metastasis in the left iliac bone (41×35×42 mm with SUVmax 17.25). In November 2022, radical treatment of the solitary bone metastasis was performed in the scope of resection of the left iliac bone with reconstructive-plastic component. According to the data of control examinations in June 2023, the patient has a complete biochemical and radiologic remission of the disease.

P933 Closing the internal opening with a rectal advancement flap increases the effectiveness of mesenchymal stem cell (MSC) injection in the treatment of complex Crohn's disease anal fistulas

Abstract Background The injection of MSCs into complex anoperineal fistulas of Crohn's disease gives a combined clinical and radiological remission of between 35 and 50% at 12 months. In our department, surgical closure is now done by rectal advancement flap (and no longer with simple stitches) in order to minimize the passage of stools and contamination of the fistula tract. The aim of this study was to compare the remission rate and the quality of life between patients treated with MSC injection using simple stitches versus a rectal flap to close the internal opening. Methods This single-center prospective study included all our consecutive patients who had a MSC injection. The first patients of the series who had closure of the internal opening(s) with stitches (2020- 2022) were compared with those who had a flap (2022-2023). Complete clinical remission was defined by complete closure of the external opening(s) without pain or discharge, and complete radiological remission by a Magnifi-CD score equal to 0 (Hindryckx P, et al. Gastroenterology 2019). Quality of Life was assessed by the Crohn's Anal Fistula Quality of Life scale (CAF-QoL) (Adegbola SO, et al. Gut 2021). Results We included 68 patients (50% women, mean age: 38 ± 13.8 years). The first 42 had stitches and the following 20 had an advancement flap (6 patients had no procedure due to an anal stenosis). The median follow-up was 12 months [6-24]. The overall complete clinical remission was 66.7% at M12: 51.1% [35.5-66.8] in the "stitches" group versus 87.5% [69.7-100.0] in the "flap" group (p = 0.005) (Figure). The difference was noticed early from M1. The mean overall Magnifi-CD MRI score decreased from 15.5 ± 4.7 to 6.5 ± 7.1 at M12 (p < 0.001) with no difference between the 2 groups. However, more patients in the flap group had a Magnifi-CD score of 0: 62.5% versus 38.2%. The CAF-QoL quality of life score improved from 51.3 ± 24.7 to 21.2 ± 20.8 at M12 (p < 0.001) with no significant difference between the 2 groups. The duration of the procedure was longer on average by 19 ± 7 minutes in the "flap" group. There was no difference in the anal incontinence score between the 2 groups. In logistic regression, the advancement flap was significantly associated with complete clinical remission (p = 0.007, HR (95% CI): 2.3 [1.3-4.3]). Conclusion Closing the internal opening with a rectal advancement flap improves the effectiveness of MSC injections with a complete clinical and radiological remission rate of 87.5% and 62.5% respectively, without consequences on anal continence.

Granulomatosis with polyangiitis: The wily masquerader of cavitary pulmonary lesions

Background: Granulomatosis with Polyangiitis (GPA) is a small and medium vessel vasculitis with predominant respiratory and renal involvement that causes florid presentation of the disease entity with varying spectrum of illness at different time intervals. Case: We report the case of a 42-years-old female patient with symptoms of low-grade fever, productive cough and significant loss of weight with multiple cavitary lesions on Chest radiograph. The patient was initially suspected to have tuberculosis which was eventually ruled out. A diagnosis of vasculitis was suspected as patient gave history of repeated hospitalisations with symptoms of upper respiratory tract involvement, left facial nerve palsy and sensorineural hearing loss, A diagnosis of limited GPA was made when the cytoplasmic Antineutrophil Cytoplasmic Antibodies, (c-ANCA) and antiproteinase-3 antibodies (anti-PR3) was elevated. The patient was treated with combination immunosuppressive therapy of prednisolone and methotrexate which induced clinical remission within one month and complete radiological remission within 4 months. Conclusion: GPA is an important non infective cause of cavitary pulmonary lesions that presents with extrapulmonary clinical spectrum (recurrent sinusitis, ear infections, renal dysfunction and neurological disease). Multifocal presentation of the disease at different time intervals results in considerable delay in diagnosis and adds to the morbidity of the disease entity.

Extended duration of treatment using reduced-frequency dosing of anti-PD-1 therapy in patients with advanced melanoma and Merkel cell carcinoma.

Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in metastatic cancers remains unclear. Many patients, especially those without radiologic complete remission, develop progressive disease after ICI discontinuation. Extending DoT with ICI may potentially improve efficacy outcomes but presents major logistical and cost challenges with standard frequency dosing (SFD). Receptor occupancy data supports reduced frequency dosing (RFD) of anti-PD-1 antibodies, which may represent a more practical and economically viable option to extend DoT. We conducted a retrospective study of patients with metastatic melanoma and Merkel cell carcinoma (MCC), who received ICI at RFD administered every 3months, after initial disease control at SFD. We evaluated efficacy, safety, and cost-savings of the RFD approach in this cohort. Between 2014 and 2021, 23 patients with advanced melanoma (N = 18) or MCC (N = 5) received anti-PD-1 therapy at RFD. Median DoT was 1.1years at SFD and 1.2years at RFD. The 3year PFS after start of RFD was 73% in melanoma and 100% in MCC patients, which compare favorably to historical control rates. In the subset of 15 patients who received at least 2years of therapy, total savings amounted to $1.1 million in drug costs and 384h saved despite the extended DoT (median 3.4years), as compared to the calculated cost of 2years at SFD. ICI administration at RFD can allow extension of treatment duration, while preserving efficacy and reducing logistical and financial burden. RFD approach deserves further exploration in prospective clinical trials.

False positive PET scan in patients with treated malignancy following COVID-19 vaccination.

e18698 Background: The COVID-19 pandemic led to mass vaccination across the globe and resulted in several unintended consequences, one of which being reactive lymphadenopathy mimicking malignancy. A large study reported hypermetabolic lymphadenopathy (HLN) in over 45% of patients after receiving at least one dose of COVID-19 vaccine. A study on breast cancer patients noted a near-400% increase in lymphadenopathy on MRI and ultrasonography over the two years prior to mass vaccination. These findings present a dilemma in patients with treated malignancy while under surveillance. As vaccination became more commonplace, a case series reported on patients with PET-detected lymphadenopathy, with biopsies confirming VRLN. These investigations contributed to general recommendations on the importance of clinical context in patient care after COVID-19 vaccination. We present a unique study that evaluates patients with treated solid and hematological malignancies that presented with HLN after COVID-19 vaccination which emphasizes the importance of clinical acumen in the management of oncological patients in the pandemic era. Methods: We identified 6 patients aged 39-95 with prior malignancy. 5 were diagnosed with metastatic melanoma, and one had a diagnosis of high-grade B-cell lymphoma. Patients were managed with chemotherapy, immunotherapy, surgery, radiotherapy, or a combination of modalities, and were in complete radiological remission. All patients received at least two doses of a COVID-19 vaccine, with one dose at least three weeks prior to a routine surveillance PET-CT. Each patient exhibited HLN. Results: Of six patients, three underwent biopsy. There was no evidence of malignancy in any biopsy, and VRLN was confirmed. The remaining patients were followed with surveillance, and all had resolution of HLN without intervention. Time between COVID-19 vaccination and PET evidence of HLN ranged from 19 to 232 days. Time between first positive and first resolved PET ranged from 92 to 463 days. All patients were alive at the time of abstract submission. Conclusions: Our study emphasizes the importance of a focused history when suspecting recurrent malignancy, especially after sustained remission in our vulnerable populations. Acknowledging that COVID-19 vaccination can lead to HLN is becoming more common, and we show that this can occur, persist, and resolve even months after vaccination. While high suspicion for recurrence should be maintained, all efforts should be taken to protect patients and prevent unnecessary procedures. Records of recent vaccinations should be available and reviewed prior to radiological studies and clinical decisions, which can reduce avoidable interventions and harm. Surveillance of our patients proved to be an appropriate approach, and our study shows that similar patient presentations can have different paths of care depending on the awareness of treating physicians.

Selective avoidance of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with HER-2 positive/triple negative breast cancer: Prospective, multi-center, single-arm study (ASLAN).

TPS624 Background: According to advanced neoadjuvant chemotherapy (NACT), which dual HER2 blockage in HER2+ BC and adding carboplatin or immunotherapy in triple-negative breast cancer (TNBC) increased pathologic complete response (ypCR) rates up to 68% and 80%. Because ypCR patients showed better survival, the indications for NACT have expanded to early BC and the expected ypCR rate has increased. Therefore, it may be reasonable to consider omitting surgery in cases with excellent responses to NACT. Several recent retrospective studies and pilot prospective studies have reported axillary pathologic complete response (ApCR) is highly correlated with breast pathologic complete response (BpCR) in HER2+ or TNBC after NACT. The current report describes the design of omission of sentinel lymph node biopsy (SLNB) after NACT in HER2+ or TNBC patients with excellent response. Similarly, EUBREAST-01 (NCT04101851) study is ongoing omission of sentinel lymph node biopsy (SLNB) after NACT in HER2+/TNBC with radiologic complete remission and a BpCR. Methods: The ASLAN trial is a prospective, multicenter, single-arm, clinical study. Five tertiary care hospitals in South Korea are participating. Inclusion criteria: women aged 20-69; cT1-3N0-1M0; HER2+ or TNBC (defined by ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC)); expected complete remission at physical examination and radiological expected Tumor size ≤ 2cm or non-mass enhancement ≤ 4cm at breast MRI after standard NACT; planned breast conserving surgery (BCS) with whole-breast irradiation; ECOG performance status 0-1. Exclusion criteria: SLNB before NACT; previous axillary surgery; bilateral BC. Patients who are eligible proceed BCS. After BCS, patients who showed BpCR are enrolled with omission of SLNB. Patients with no BpCR proceed with routine axillary surgery. The assumption for acceptable 5-year RFS ≥84% is based on previous study findings. The calculated total case number for per- protocol analysis is N=178. Primary endpoint: 5-year recurrence free survival. Secondary endpoint: local recurrence free survival, breast cancer specific survival, overall survival, ipsilateral axillary recurrence interval, distant metastasis free survival, contralateral breast free survival, re-operation rate according to breast biopsy after NACT, adverse event, and quality of life. The first patient was enrolled on September 2021. Among 147 patients who screened, 106 patients have been enrolled in January 2022. We plan to complete the target accrual by December 2025. Clinical trial information: NCT04993625 .

An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report

BackgroundWe present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease.Case presentationAn 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease.ConclusionsIn the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the “healthy” adrenal tissue residue than a direct secretory activity by the adrenal tumor.

A Case Series of Metastatic Breast Cancer Patients in Prolonged Remission who Discontinued Maintenance Anti-HER2 Treatment

Purpose: Patients with HER2-positive metastatic breast cancer (MBC) remain on long-term maintenance anti-HER2 treatment for many years, despite showing radiological complete remission (rCR) or stable disease (rSD). There is currently no consensus regarding discontinuing anti-HER2 treatment in this context, with associated risk of cardiotoxicity, impact on quality of life and cost implications. We present a case series of HER2-positive MBC patients with rCR or rSD who remained off treatment with a durable response and compared outcomes with patients on continuous anti-HER2 treatment for at least 5 years.

Abstract OT1-07-01: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 36 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2023 -Primary outcome analysis: Q1/2027 Current accrual: In June 2022, 150 patients were recruited in Germany and Italy. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy) Citation Format: Toralf Reimer, Thorsten Kuehn, Angrit Stachs, Anke Kleine-Tebbe, Nikola Bangemann, Andrea Stefek, Carolin Hammerle, Jörg Heil, Antje Nixdorf, Gabriele Bonatz, Agnieszka Nolte, Isabel T. Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Davide Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-07-01.

Obinutuzumab Plus Chemotherapy As First Line Treatment in Patients with Follicular Lymphoma: Experience from a Community Hospital

Background The combination of Obinutuzumab plus chemotherapy (Obi-chemo) regimen is currently one of the standard first-line treatments available for patients diagnosed with follicular non-Hodgkin's lymphoma (FL). The aim of our study is to evaluate the efficacy and safety of the Obi-chemo regimen in a community hospital setting. Methods Retrospective analysis of patient's medical records admitted to our hospital with a confirmed pathologic diagnosis of FL that were treated with the regimen of Obi-chemo as first-line treatment. Between January 1, 2017 and January 5, 2022, a total of 10 consecutive patients met the criteria for evaluation. Results The baseline characteristics of the patients evaluated are as follows: The group consisted of 7 males and 3 females. Median age in years was 56 (range 43-80). 10% (n=1) patients had stage 2, and the remaining 90% (n=9) had stage III-IV. Bone marrow involvement was noted in 70% (n=7) and 40% (n=4) had bulky mass >7 cm at presentation. Of the total ten patients, 60% (n=6) received Obinutuzumab plus Bendamustine and the remaining 40% (n=4) received Obinutuzumab plus CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). All patients required G-CSF support. After completion of chemotherapy, 7 patients achieved a complete clinical and radiologic remission whereas 3 patients achieved a partial remission. Of these last 3 patients, two went on to achieve a complete remission during follow-up. Of the 7 patients who achieved an initial complete remission, one subsequently did relapse during follow-up. While on treatment, neutropenia and thrombocytopenia were documented in all 10 patients. 40% (n=4) of patients developed neutropenic fever, and 10% (n=1) developed grade 3 thrombocytopenia. 50% (n=5) of patients developed grade 1-2 infusion-related adverse events (nausea, hypertension, headache and skin rash). Two patients required chemotherapy de-escalation due to toxicity. No long-term toxicity or treatment-related deaths were reported. Conclusions Our study supports the findings of the pivotal clinical trials that led to the approval of the Obi-chemo antineoplastic regimen as first-line treatment for patients with FL by the regulatory agencies in Europe (EMA) and North America (FDA).

Clinical implication of radiologic complete remission on Crohn’s Disease: Compared with endoscopic remission

ObjectivesTo determine the clinical implications of radiologic complete remission (CR) in Crohn’s disease (CD) evaluated by computed tomography (CT) or magnetic resonance enterography (MRE) in comparison with endoscopic CR. MethodsTwenty-five CD patients who achieved endoscopic CR after medical treatment were retrospectively enrolled in this study. All patients underwent ileocolonoscopy, CT, or MRE at baseline, at the time of endoscopic CR, and during follow-up. Two radiologists assessed the mural and perienteric abnormalities on pre- and post-treatment CT or MRE in consensus. Patients were divided into radiologic CR and non-CR groups at the time of endoscopic CR. CD recurrence during subsequent follow-up periods was evaluated using clinical, laboratory, and CT/MRI findings. Statistical analysis was performed to assess whether there were significant differences in patient outcomes between the groups. ResultsAt the time of endoscopic CR, nine patients (mean age, 36.6 years) showed normalization of all radiologic features and were designated as the radiologic CR group. However, 16 patients (mean age: 32.9 years) showed residual CT/MRE abnormalities, suggesting persistent active inflammation, and were designated as the radiologic non-CR group. During follow-up, there was a significant difference between the groups regarding clinical outcomes (deep CR, 8/9 vs 5/16, P = 0.011; CD recurrence, 1/9 vs 14/16, P < 0.001). The mean fecal calprotectin level was significantly lower in the radiologic CR group (287.5 ug/g) than in the non-CR group (652.4 ug/g) (P = 0.023). ConclusionsRadiologic CR can represent a better therapeutic endpoint in CD, showing superiority over endoscopic CR in predicting both clinical and biochemical outcomes.

Discontinuation of imatinib in patients with oligo-metastatic gastrointestinal stromal tumor who are in complete radiological remission: A prospective multicenter phase II study.

11535 Background: Life-long tyrosine kinase inhibitor (TKI) treatment is recommended for patients (pts) with metastatic GIST. We investigated whether highly selected pts with metastatic GIST may remain in durable complete remission after imatinib discontinuation. Methods: In this 1-group, prospective, multicenter phase II trial (NTC02924714) selected pts with overtly metastatic GIST discontinued imatinib treatment. Eligible pts had been treated with imatinib &gt; 5 yrs for oligo-metastatic (≤3 metastases) disease, had no GIST progression and had undergone either R0/R1 resection or radiofrequency ablation (RFA) of all metastases, and had no longer detectable metastases on CT/MRI imaging, The primary endpoint was 3-yr progression-free survival (PFS), overall survival was a secondary endpoint. We estimated to achieve an improvement from 15% to 35% in 3-yr PFS compared to pts treated in the BRF-14 trial with a sample size of 31 pts. Results: The trial closed early due to slow accrual. Between January 5, 2017, and June 5, 2019, 12 pts (males, 7) with a median age of 67 yrs (range, 50-85) were enrolled. All pts had their primary tumor surgically removed (stomach, 4; small bowel, 6; large bowel/rectum, 2). Seven pts had KIT exon 11 mutation, 2 KIT exon 9 mutation, 1 PDGFRA exon 12 mutation, 1 had no mutation in KIT/PDGFRA, and 1 pt had unknown GIST mutational status. Eight pts had liver metastases, 3 peritoneal metastases, and 1 had both. Prior to enrollment all pts were in macroscopic complete remission after surgical metastasectomy (n = 7), RFA (n = 2), or both (n = 1), and 1 pt achieved complete radiological response with imatinib. At enrollment, 8 pts had imatinib 400 mg/d and 4 had &lt; 400 mg/d. The median time of imatinib treatment before study entry was 8 yrs (range, 5-17). After imatinib discontinuation 7 (58%) pts progressed; the median time to progression was 10 mos (range, 2-31 mos). Five (42%) patients were progression-free after a median follow-up time of 42 mos (range, 30-59 mos). Median PFS was 23 mos and the estimated 3-year PFS 39%. Patients who progressed all achieved a second remission after restarting imatinib and were alive after a median follow-up time of 48 mos (range, 32 to 61 mos). Conclusions: The findings suggest that discontinuation of imatinib is safe in highly selected patients with oligo-metastatic GIST and that such patients may survive without detectable GIST progression for several years. The findings need to be viewed with caution due to the small pt numbers. Further study on imatinib discontinuation seem warranted. Clinical trial information: NCT02924714.

The Role of Neuroaxis Irradiation in the Treatment of Intraspinal Ewing Sarcoma: A Review and Meta-Analysis.

Simple SummaryPrimary extraosseous intraspinal Ewing sarcoma (EwS) is a rare disease and optimal treatment strategies remain unclear. Most patients undergo trimodal therapy consisting of surgery, chemotherapy and radiation therapy. In this study, we focus on the role of radiation therapy in the treatment of EwS, specifically the use of craniospinal irradiation (CSI). We identified 24 patients with intraspinal EwS treated with CSI. A majority of these patients achieved complete remission. We found that patients with multiple lesions at time of diagnosis and intradural tumor location were more likely to undergo CSI while patients with a single lesion received focal irradiation more often. In spite of this imbalance, there was no difference in survival outcome between treatment groups. In summary, CSI is a valuable option in the treatment of EwS and should be considered individually based on tumor and patient characteristics.The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p < 0.001). Despite over-representation of these unfavorable characteristics, there was no survival difference between groups (p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials.

Combined immune checkpoint blockade and radiotherapy induces durable remission in relapsed natural killer/T-cell lymphoma: a case report and review of the\xa0literature

BackgroundExtranodal natural killer/T-cell lymphoma is a rare, aggressive non-Hodgkin lymphoma that is treated upfront mostly with L-asparaginase containing regimens. Relapsed extranodal natural killer/T-cell lymphoma is associated with a poor prognosis, and there is no established standard of care.Case presentationWe report the case of a 72 year-old white male with a distant extranasal relapse of extranodal natural killer/T-cell lymphoma that has been managed successfully with a combination of radiation and immune checkpoint blockade with pembrolizumab. Pseudoprogression with new skin and bone lesions on positron emission tomography imaging was encountered during this Caucasian patient’s immunotherapy and was successfully managed with supportive care and continuation of immune checkpoint blockade.ConclusionsThe patient has been in complete clinical, radiologic, and molecular remission for close to 3 years and has not had any immune-related adverse effects. Pseudoprogression is a clinical challenge that can be encountered while patients are treated with immunotherapy, and astute clinical acumen is needed for accurate management. We believe this is the longest duration of response to immune checkpoint blockade in relapsed extranodal natural killer/T-cell lymphoma reported to date in literature. There is a strong biologic rationale in combining radiation with immunotherapy. The optimal timing, dose, and duration of radiation combined with immunotherapy in extranodal natural killer/T-cell lymphoma need to be prospectively evaluated.

Value of tube combined with real-time ultrasound-guided accurate interstitial high-dose-rate brachytherapy for post-operative pelvic side-wall recurrences of cervical cancer.

PurposeTreatment of post-operative pelvic side-wall relapses of cervical cancer has always been a therapeutic challenge for radiation oncologists. Radiation dose boost to recurrent tumor by brachytherapy is necessary, but difficult to achieve. Our treatment center has successfully achieved precise transvaginal insertion of a pelvic side-wall mass, using a metal tube with real-time ultrasound guidance. This study investigates the efficacy and safety of image-guided high-dose-rate (HDR) interstitial brachytherapy (IBT) for patients with post-operative pelvic side-wall relapses.Material and methodsBetween 2018 and 2020, 36 post-operative pelvic side-wall relapses of cervical cancer patients receiving external beam radiotherapy (EBRT) combined with HDR-IBT were analyzed retrospectively. Doses per fraction ranged from 6.0 to 7.0 Gy, whereas cumulative equivalent doses in 2 Gy fractions ranged from 80 to 100 Gy. Effects of prognostic factors on local control (LC) and progression-free survival (PFS) were analyzed, and late toxicity data were evaluated.ResultsA total of thirty-six patients were included, with a median follow-up of 19.3 months. The tumor response was obtained for all patients, with radiological complete remission in 20 (55.6%) patients. Two-years LC and PFS rates were 72.2% and 47.2%, respectively. Grade II rectal toxicity was observed in 5 patients (13.9%). Multivariate analyses for LC and PFS using proportional regression model were performed, in which shape of exophytic tumor was associated with a significantly better prognosis for both LC and PFS (HR = 0.071, 0.128, p = 0.005, 0.002). Clinical target volume (CTV) D90 remained associated with a significantly better prognosis for PFS (HR = 0.056, p = 0.000).ConclusionsA metal tube placed in the vagina, under the guidance of real-time ultrasound in transvaginal IBT for pelvis masses can be accurately achieved. The shape of exophytic tumor and CTV D90 were associated with a significantly better prognosis for PFS, and the shape of exophytic tumor was also associated with a better prognosis for LC. Therefore, radiation dose boost using IBT can improve the prognosis of patients with post-operative pelvic side-wall recurrences of cervical cancer.

Remission of Pediatric Diffuse Intrinsic Pontine Glioma: Case Report and Review of the Literature.

ABSTRACTBackground:Diffuse midline glioma (DMG) is one of the most aggressive pediatric tumors. Approximately 60% of pediatric DMG patients die within the first year of diagnosis. Complete clinical and radiological remission of DMG is extremely rare. The objective of this study was to describe a case of remission of pediatric DMG and to compare with similar cases published so far.Results:DMG was diagnosed in a 2-year-old girl who presented with brainstem and increased intracranial pressure manifestations. Ventriculoperitoneal shunt and chemotherapy-based treatment were offered. From the diagnosis, in spite of progressive enlargement of the tumoral lesion, her clinical condition improved remarkably. After the end of chemotherapy, progressive and gradual imagiological improvements occurred. At the end of the 60th month of follow-up, she was asymptomatic with total remission. Six pediatric DMG cases, from birth to the age of 3, in whom remission occurred were found in the literature. Histology sample was available in two of them (fibrillary astrocytoma—WHO Grade II and anaplastic astrocytoma—WHO Grade III). None received chemotherapy or radiotherapy.Conclusion:Remission of pediatric DMG is extremely rare and reinforces the biological heterogeneity of the tumor. In the absence of reliable predictors of prognosis, offering the best supportive treatment, including neurosurgical interventions should be considered in similar cases.

Complete response of metastatic cervical adenocarcinoma treated with chemoradiotherapy followed by pembrolizumab: A case report

Introduction: Metastatic adenocarcinoma of the uterine cervix is challenging to treat, particularly if there is persistent disease following surgery and chemoradiotherapy. In recent years, advances in checkpoint inhibitor-based immunotherapy have shown promise in patients in a variety of cancers. Only limited information is available concerning treatment of cervical adenocarcinoma with checkpoint inhibitors. Case Report: This case report details a patient with metastatic cervical adenocarcinoma with persistent disease following surgical resection. Subsequent treatment with cisplatin, paclitaxel, and bevacizumab therapy with concurrent radiotherapy resulted in a partial response. The patient was subsequently treated with pembrolizumab. After 3 cycles of treatment the patient achieved a stable radiologic complete remission, which continues after treatment discontinuation. Conclusion: This result suggests that chemoradiotherapy with either concurrent or sequential administration of a PD-1 antibody, such as pembrolizumab, may have significant activity as treatment of metastatic or unresectable cervical adenocarcinoma. Further prospective clinical testing appears warranted.