Previous Radiation Field Research Articles

NFS-19. ATYPICAL PRESENTATION OF GLIOMAS IN ADOLESCENTS WITH NEUROFIBROMATOSIS TYPE 1 (NF1): A CASE SERIES

Abstract BACKGROUND Patients with NF1 are at risk for developing gliomas, usually low-grade in childhood but may be high-grade in adults. In children, the most common sites of disease are the optic pathway and brainstem; tumors in these regions often arise in young children and display histological features characteristic of pilocytic astrocytoma (PA) when biopsied. Typical MRI findings include T2 hyperintense, T1 hypointense lesions with minimal contrast enhancement and no diffusion restriction. Due to the well-established pattern of low-grade tumor formation in children with NF1, as well as the surgically challenging areas in which these tumors develop, low-grade glioma (LGG) therapy is often initiated without histologic confirmation of the diagnosis in classic cases. In cases with atypical disease location, older age at presentation or imaging appearance, a biopsy may be considered to exclude higher-grade lesions. METHODS Retrospective chart review, case series RESULTS Four adolescent patients with NF1 presented with atypical suspected gliomas. All four patients underwent surgical biopsy/resection. Case 1 was a left temporal lesion in the previous radiation field for optic pathway glioma; biopsy confirmed LGG with MAP2K1 mutation and increased focal proliferation index (28%), but methylation did not match with any established classification. The patient progressed through multiple rounds of therapy and succumbed to her tumor. Case 2 was a left occipital lesion; biopsy confirmed PA with CDKN2A deletion. The tumor displayed rapid regrowth, but subsequently stabilized. Case 3 was a right frontal lesion; confirmed PA. The tumor demonstrated some regrowth but then stabilized. Case 4 was a basal ganglia lesion; confirmed PA. The patient has demonstrated stable MRI findings and has not required further intervention. CONCLUSIONS Biopsy yielded helpful prognostic information (additional mutations, proliferation rate) in half of these atypical cases. Biopsy should be carefully considered for NF1 patients with atypical presentation or a history of radiation.

Re-irradiation for recurrent cervical cancer: A single institutional experience

PurposeSalvage treatment of recurrent cervical cancer of patients with a history of radiotherapy is currently a major clinical challenge. The purpose of our study was to retrospectively analyze clinical outcomes of radiation in patients with recurrent cancer who have previously received radiotherapy at our hospital and further explore the efficacy and safety of this treatment modality. MethodsAll consecutive patients who underwent re-irradiation were included in our department between January 2015 and December 2017. All the patients received Volumetric Modulated Arc Therapy (VMAT) alone or VMAT followed by three dimensional–image-guided brachytherapy (3D-IGBT). The volume and dose for re-irradiation depended on previous radiation fields, dosimetry and recurrence sites. All patients received systemic chemotherapy before or after re-irradiation. ResultsFifty patients were included in our study. The median time from primary radiotherapy to re-irradiation was 12 months. Local recurrence, which was the most common failure following primary treatment, was present in 25 patients (50.0 %) while regional recurrence, loco-regional recurrence and distant recurrence combined in-filed recurrence was present in 8 (16.0 %), 9 (18.0 %) and 8 patients (16.0 %). Re-irradiation dose to lymph nodes was 45 Gy with or without a boost up to 55–60 Gy, and to the gross mass was 36–45 Gy with or without a boost up to 45–61 Gy. The median follow-up period was 22 (range,4–59) months. The 3-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 58.0, 38.7, and 44.4 %, respectively. The median time of PFS and OS was 14 and 26 months, respectively. The interval between two successive radiotherapies beyond 12 months was significantly associated with better LC and PFS (p ≤ 0.05), but without the benefit of OS (p > 0.05). Serum SCC antigen level less than 1.5 ng/ml had a significantly better impact on PFS (p ≤ 0.05). Overall, 14 patients (28 %) experienced ≥ grade 3 acute toxicities, while 9 (18 %) experienced ≥ grade 3 late toxicities. ConclusionsRe-irradiation with VMAT is an effective and safe salvage treatment option with a reasonably good clinical outcome and toxicity profile in selected patients. In our experience, recurrent cancer patients with an interval between two successive radiotherapy courses beyond 12 months and with a serum SCC-Ag level less than 1.5 ng/ml, had improved outcomes.

CPC02 Delayed widespread lichenoid drug reaction with radioisotopic response in a patient treated with nivolumab

Abstract The introduction of immune checkpoint inhibitors for the treatment of a wide variety of malignancies has led to a rise in cutaneous immune-related adverse events (irAEs), including autoimmune and autoinflammatory skin conditions, which typically present within the first 16 weeks of treatment—on average, 3.6 weeks after drug initiation. Cutaneous irAEs occur in approximately 8.7% of patients receiving antiprogrammed cell death type 1 therapy (PD-1). Nivolumab is an antibody against PD-1 widely used for various cancers. As the application of these therapies expands, understanding of their adverse cutaneous effects is essential. We present a 76-year-old woman with metastatic renal cell carcinoma, who developed a widespread pruritic eruption 18 months after commencing nivolumab. Examination revealed a papular and vesicular rash affecting the arms, legs, anterior chest, face, hands and feet. There was a confluent well-demarcated rectangular area of grouped papules on the right side of her back; this site had been treated with radiotherapy for localized rib metastases 1 month prior to onset of rash. There was no mucosal involvement and no systemic symptoms. Three skin biopsies were taken, which showed vacuolar alteration of the basal layer and a band-like inflammatory cell infiltrate at the dermoepidermal junction, with focal areas of subepidermal separation. Direct immunofluorescence was negative, and skin swabs were negative for bacterial and viral infection. A diagnosis of delayed bullous lichenoid drug reaction secondary to nivolumab was made. The area involving the previous radiotherapy field was considered to be a radioisotopic response rather than a radiation recall response as she was already on nivolumab when it occurred. She discontinued nivolumab and commenced oral prednisolone and her skin settled over 5 weeks. Lichenoid dermatitis is a known adverse reaction associated with PD-1 therapy, with improved survival outcomes noted in patients with lichenoid irAEs on PD-1 therapy. Typically, it occurs within 16 weeks, with a documented range of 1–266 days. This patient developed a delayed lichenoid eruption at approximately 550 days, with concurrent radioisotopic response at a previous radiotherapy site. Radiotherapy-induced lichen planus is rare, with only one case report documenting involvement outside the irradiated field. We found no previous reports of nivolumab causing lichenoid drug eruption after such a protracted period. This case adds to the growing literature around PD-1 inhibitor-associated cutaneous eruptions.

Cutaneous Radiation-Associated Angiosarcoma After Treatment of Carcinoma Penis: First Report from Tertiary Cancer Centre of North India.

Cutaneous radiation-associated angiosarcoma (cRAA) is a rare and aggressive secondary cutaneous angiosarcoma (cAS) with poor survival. cRAA has been mostly reported in breast carcinoma patients. Owing to its rarity, there is scanty literature available and no treatment guidelines. To the best of our knowledge, this is the first report of cRAA after multimodality treatment of carcinoma penis. A sixty-eight-year-old gentleman, a known case of carcinoma penis, underwent total penectomy with perineal urethrostomy and bilateral radical inguinopelvic lymph node dissection 6 years ago. He received adjuvant radiotherapy to the pelvis and bilateral groin. He presented with a bleeding plaque-like lesion with ulceration over the left lower abdomen (within previous radiation field) which rapidly progressed in size over the past 2 months. On examination, the lesion bled profusely on touch. Contrast MRI was suggestive of lobulated exophytic enhancing cutaneous lesion free from underlying muscle. Wedge biopsy was suggestive of cutaneous angiosarcoma. He underwent wide local excision with local perforator flap reconstruction from the right lower abdomen. Histopathology was suggestive of cutaneous angiosarcoma which showed immunoexpression of CD31, ERG1, cMYC suggestive of cRAA. cRAA is a very aggressive disease with 5-year survival of15-34%. To the best of our knowledge, this is the first ever reported case of cRAA of lower abdomen after multimodality management of carcinoma penis. It masquerades with other benign and less aggressive radiation-induced skin lesions. cMYC immunoexpression is specific for secondary cAS. Wide local resection with negative margin provides the best outcome.

Post-irradiation sarcoma after definitive radiation therapy for nasopharyngeal carcinoma

Background and purposePostirradiation sarcoma (PIS) is a rare radiation-induced malignancy after nasopharyngeal carcinoma (NPC) treatment. Materials and methodsWe retrospectively screened 9,185 NPC patients between 2000 and 2020 and identified 41 patients with PIS according to the modified Cahan’s criteria: (1) the PIS must have arisen within a previous radiation field; (2) a latent period must have existed; (3) histologically proved sarcoma; (4) the tissue in which the PIS arose must have been healthy prior to the radiation. The initial radiation therapy techniques used were 2D (25; 61.0%), 3D (7; 17.1%), and IMRT (9; 22%). ResultsThe time (year) from radiotherapy (RT) to PIS was longer when using 2D or 3D irradiation techniques (median, 14.2; range, 3.4–28.1; Q1-Q3, 8.6–19.7) than when using IMRT (median, 6.6; range, 3.8–15.7; Q1-Q3, 4.5–11.7; P =.026). The time (year) from RT to PIS diagnosis was significantly longer when using lower radiation energy from cobalt-60 (median, 15.8; range, 10.4–28.4; Q1-Q3, 12.5–23.8) than when using a higher radiation energy of 6 or 10 MV (median, 10.2; range, 3.4–23.3; Q1-Q3, 6.5–16.1; P =.006). The 2-year overall survival rates for patients who underwent surgery, radical radiotherapy, systemic therapy alone and no treatment were 60.7 %, 42.9 %, 0 % and 0 %, respectively (P =.000). Of the 3 retrievable initial RT dosimetry plans for NPC, the D95 values (dose that covers 95 % of the PIS volume) for PIS were 6267, 6344 and 5820 cGy, respectively. ConclusionHigh radiation energy and modern techniques may shorten NPC PIS latency. Surgery may be associated with improved survival if feasible.

Nivolumab-induced radiation recall pneumonitis in non-small-cell lung cancer patients with thoracic radiation therapy.

The role of previous thoracic radiation therapy as a risk factor of immune-related pneumonitis is unclear. Furthermore, some patients develop radiation recall pneumonitis, which is characterized by a radiation pneumonitis-like imaging pattern with consolidation progressing within a previous radiation field. In this multicenter retrospective study, we analyzed the relationship of previous thoracic radiation therapy with immune-related pneumonitis and the characteristics of radiation recall pneumonitis. The medical records of patients with non-small-cell lung cancer who had received nivolumab between December 2015 and March 2017 at five institutions were retrospectively reviewed. Incidence, imaging patterns, clinical course, and risk factors of immune-related pneumonitis and radiation recall pneumonitis were evaluated. A total of 669 patients were evaluated, and the incidences of all-grade and grade 3 or higher immune-related pneumonitis were 8.8% and 2.6%, respectively. The incidences of immune-related pneumonitis were 13.2% (34/257) and 6.1% (25/412) in patients with and those without previous thoracic radiation therapy, respectively. A history of previous thoracic radiation therapy was associated with immune-related pneumonitis (odds ratio, 2.11; 95% confidence interval, 1.21-3.69 in multivariate analysis). Among the patients with previous thoracic radiation therapy, 6.2% (16/257) showed radiation recall pattern. This study found an increased risk of nivolumab-induced immune-related pneumonitis associated with a history of thoracic radiation therapy. Radiation recall pattern was one of the major patterns of immune-related pneumonitis among the patients with previous thoracic radiation therapy. Incidence, risk factors, and clinical outcome of radiation recall pneumonitis were elucidated.

Long-term Follow-up of CD20-directed Chimeric Antigen Receptor Adoptive T-cell Therapy

Chimeric antigen receptor (CAR) T cell therapy targeting B-cell antigens has led to unprecedented success in inducing complete response (CR) rates in refractory B-cell non-Hodgkin lymphomas (NHLs). We previously reported the results of a pilot trial testing a 3rd generation CAR with 4-1BB and CD28 costimulatory domains targeting CD20 in patients (pts) with relapsed B-cell lymphomas (NCT00621452). 3 pts received cyclophosphamide (CY) 1 g/m2 IV for lymphodepletion 2 days prior to a series of 3 CAR T cell infusions 2 to 5 days apart in escalating doses followed by 2 weeks of low-dose IL-2. Here, we report the long term follow up of 2 of these pts. The third pt, UPN-02, died of progressive mantle cell lymphoma (MCL) and myelodysplastic syndrome at ~26 months (mos) post-treatment. Pt UPN-03, with relapsed MCL, had no evaluable disease after an excisional biopsy following protocol therapy. He relapsed after 2 years with a left flank mass, which was then radiated. He was re-treated with CY lymphodepletion, a dose of 1.8 x 109 CAR T cells/m2, and low-dose IL-2. At 6 weeks post infusion, he developed a small mass at the margin of his previous radiation field suspected to be recurrent MCL. This mass spontaneously regressed 1 mo later. Subsequent CT scans showed a residual soft tissue mass that gradually decreased over time and met criteria for CR by CT criteria. He remained in remission, albeit with detectable minimal residual disease (MRD) by ClonoSEQ assay, for the next 8.4 years until developing a subcutaneous chest mass and axillary adenopathy with biopsy showing recurrent MCL. Pt UPN-04, with relapsed follicular lymphoma (FL), had stable disease by CT at 1 mo but went on to have a partial response at ~3 mos. By 12 mos post-CAR T treatment there was evidence of progressive disease. However, between 2.5 and 3 years post-treatment he experienced resolution of all palpable nodes, and a near-CR was confirmed by CT at 35 mos after treatment. He remained without any clinical signs of progression with low level MRD by ClonoSEQ for the next 4 years. At 7.2 years post-CAR T cell treatment, he was found to have recurrent FL. CAR T cells were detectable for up to 12 mos in UPN-03 and 9 mos in UPN-04 by qPCR assay. B-cell recovery over time in both pts confirmed a lack of functional CAR T cell persistence. Given these findings, along with the durable responses observed in both pts, we hypothesized that these late remissions were caused by endogenous immune responses triggered by CAR T cell therapy. To evaluate this, we performed western blot assays incubating post-infusion serum with autologous tumor cell lysates followed by incubation with an anti-human IgG antibody, which showed new bands at post clinical response timepoints in both pts. ELISPOT assays with PBMCs co-incubated with autologous tumor cells exhibited spikes in IFN-γ secreting cells compared with control cells at timepoints proximal to their clinical responses. These findings suggested the occurrence of both humoral and cellular anti-tumor responses. To better characterize the T-cell response, we performed high-throughput TCR-β sequencing (Adaptive ImmunoSEQ) for UPN-04. We conducted a differential abundance analysis to identify possible tumor-reactive T cells, with the hypothesis that tumor-reactive T cell clones would be increased near the timepoints with clinical responses at ~3 and 35 mos. We identified 12 and 7 sequences, respectively, at these timepoints that were significantly increased compared to baseline (FDR < 0.05) and not present in the CAR-T product; 3 sequences were present at both 3 and 35 mos, and 1 of these was also significantly enriched in a post-infusion tumor biopsy, suggesting possible tumor-specificity. These results support the hypothesis that the late responses were mediated by endogenous T cells rather than CAR T cells. In summary, we report long-term remissions in 2 of 3 pts treated with CD20-targeted CAR T cell therapy, with evidence of endogenous anti-tumor immune responses. Together with previously published reports of epitope spreading after CAR-T for solid tumors, and in mouse models of lymphoma, these results suggest that CAR T cells have the capacity to elicit endogenous anti-tumor immune responses in lymphoma. Our use of CY without fludarabine as lymphodepletion may have facilitated such responses. Future research is warranted to enhance epitope spreading after CAR-T therapy as a bulwark against escape by antigen loss or loss of CAR-T persistence.

Case report: Triple whammy: Synchronous radiotherapy induced glioblastoma multiforme and papillary thyroid cancer following nasopharyngeal carcinoma

Secondary malignancies following radiotherapy are well documented, with an estimated incidence of 5%. These may manifest as carcinomas, gliomas, or sarcomas within the previous radiation field. Glioblastoma multiforme following radiotherapy for nasopharyngeal carcinoma is an uncommon occurrence and carries a poor prognosis, whereas papillary thyroid carcinoma following radiotherapy is well documented, though the exact incidence is not well documented. The occurrence of synchronous radiotherapy-induced malignancy over both sites has not been described in the literature before. We describe a middle-aged gentleman diagnosed with glioblastoma multiforme and papillary thyroid carcinoma 6 years after radiotherapy for nasopharyngeal carcinoma. Though our case is the first reported case of a synchronous tumour of its nature, it is likely that such cases are under-reported. Long-term vigilance for loco-regional radiotherapy-induced secondary malignancies is a must, and the presence of a second distinct secondary malignancy must be entertained.

MSS02 Presentation Time: 3:50 PM: Feasibility of 3D-Printed Endorectal High Dose Rate Brachytherapy Applicator: A Single Patient Case Report

<h3>Purpose</h3> Endorectal brachytherapy is an effective treatment for select patients with rectal cancer, particularly in re-irradiation cases. In the United States, this technique is underutilized. Herein we describe, to our knowledge, the first report of a previously irradiated rectal cancer patient treated with a 3D-printed Endorectal High Dose Rate Brachytherapy Applicator. <h3>Materials and Methods</h3> A 64 year old morbidly obese female who was previously irradiated for endometrial cancer in 2009 presented with newly diagnosed uT3N0, MRI T2N0 rectal adenocarcinoma. Previous radiation records were no longer available other than a treatment summary identifying a total dose of 50.4 Gy in 28 fractions was delivered to the pelvis. Total neoadjuvant therapy was recommended with a watch and wait approach given surgical difficulties in a morbidly obese woman previously irradiated. The mass began 3 cm from the anal verge, extended nearly 5 cm superiorly, and circumferentially involved less than 50% of the rectal lumen. Fiducial markers were placed in the 4 cardinal directions. A 2.5 cm diameter, 18 cm length, 13 multichannel applicator (1 central channel, and 12 outer channels 5mm from cylinder surface) design was designed in <i>Autodesk Fusion 360</i> to ensure adequate coverage (see figure 1). 3D printing was achieved with a FormLabs 3 printer using Surgical Guide V1 resin. [JF1] The applicator was placed on the first day of treatment at CT simulation. The patient was placed in the prone position with the applicator inserted in the rectum. Treatment was delivered in 4 consecutive daily fractions of 6.5 Gy for a total of 26 Gy. <h3>Results</h3> The CTV volume was 19.8 cc and maximum tumor depth was 13 mm. Tumor coverage was excellent with a V200 of 6%, V150 of 23%, V100 of 70%, D90 of 83%. Target coverage was sacrificed to reduce the V200, given unknown previous radiation fields. The bladder D2cc dose was 5.4 Gy[JD2] [MS3] . The patient had complete resolution of rectal bleeding by the 4^th fraction. She reported no acute toxicities. At the time of this report, the patient is 1 month post brachytherapy with no reported toxicities with significantly easier bowel movements and continues to have no bleeding. <h3>Conclusion</h3> To our knowledge, this is the first reported 3D printed Endorectal High Dose Rate Brachytherapy Applicator used in clinical practice. In this case, the patient had early response with no adverse events. We believe 3D printing is a useful tool for Brachytherapists, and a feasible treatment option for rectal cancer patients.

Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer.

This study evaluated the toxicity associated with radiation techniques on curative re-irradiation (re-RT) in patients with thoracic recurrence of non-small cell lung cancer (NSCLC). From 2011 to 2019, we retrospectively reviewed the data of 63 patients with salvage re-RT for in-field or marginal recurrence of NSCLC at two independent institutions. Re-RT techniques using X-ray beams and proton beam therapy (PBT) were also included. Re-RT had a 2-year overall survival (OS) and local progression-free survival of 48.0% and 52.0%, respectively. Fifteen patients experienced grade 3 or higher toxicity after re-RT. The complication rates were 18.2% (4/22) and 26.8% (11/41) in PBT patients and X-ray patients, respectively. Airway or esophageal fistulas occurred in seven patients (11.1%). Fistulas or severe airway obstruction occurred in patients with tumors adjacent to the proximal bronchial tree and esophagus, who underwent hypofractionated radiotherapy (RT) or concurrent chemotherapy, and with a higher dose exposure to the esophagus. In conclusion, salvage re-RT was feasible even in patients with local recurrence within the previous RT field. PBT showed similar survival outcomes and toxicity to those of other techniques. However, thoracic re-RT should be performed carefully considering tumor location and RT regimens such as the fraction size and concurrent chemotherapy.

Toxicity and Survival Outcomes From Intensity Modulated Proton Therapy-Based Re-Irradiation in Patients With Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Cumulative radiation doses to organs-at-risk is the primary limiting factor when delivering thoracic reirradiation (reRT). Intensity-modulated proton therapy (IMPT) offers a unique dosimetric advantage allowing for dose-escalation while limiting normal tissue irradiation. Given the limited published data, we analyzed toxicity and survival outcomes of non-small cell lung cancer (NSCLC) patients with prior radiation history undergoing IMPT-based definitive reRT. <h3>Materials/Methods</h3> A single-institution retrospective IRB-approved analysis was conducted of 62 consecutive patients treated with IMPT-reRT between from 2016-2020. Median dose of prior RT was 60.2 Gy EQD2 (range 30-126 Gy EQD2). Median time between initial and reirradiation courses was 30 months (range 3.5 – 562 months). Median IMPT-reRT dose was 62.2 Gy (RBE) EQD2 (range 40.1 – 99.7 Gy RBE EQD2). Patients received conventionally fractioned (n=37), twice-daily (n=6), or hypofractionated (n=19) reirradiation. The majority had full overlap with the previous radiation field (N=49, 79%), were centrally located (N=42, 58%), and involved nodal irradiation (N=47, 76%). Concurrent chemotherapy was delivered in 27 (44%) patients. Treatment related toxicities were analyzed in relationship to re-RT dosimetric parameters in 30 patients whose initial RT plan was available. Kaplan-Meier method and Cox Proportional Hazard was used to estimate overall survival (OS) and freedom from local progression (FFLP) calculated from the start of reRT. <h3>Results</h3> Grade 3 acute toxicities were seen in 6 (9%) patients (pulmonary [N=3], esophageal/skin/fatigue [N=1 each]). With a median follow-up from the start of reirradiation of 12.5 months, 8 (13%) patients experienced a grade 3 late toxicity (esophageal [N=4], pulmonary [N=3] and cardiac [N=1]). Two (3%) grade 5 toxicities were observed. None of the analyzed dosimetric parameters (lung, heart, esophageal, target) correlated with grade 3 or more toxicity. CTV size greater than 150 cm³ exhibited a trend of association with grade 3+ toxicity HR = 3.2 (95% CI: 0.88 – 12.1; p=0.08). Median FFLP was not reached and median OS was 22.6 months (95% CI, 16.5 – 22.1 months). On univariate analysis variables associated with improved OS were higher reirradiation dose, cumulative radiation dose >135 Gy, and smaller CTV (< 150 cc). However, on MVA only CTV size retained statistical significance (HR = 3.56; 95% CI, 1.10 – 11.48; p=0.03). <h3>Conclusion</h3> This is the largest series to date reporting outcomes for NSCLC patients treated with IMPT-reRT which demonstrated acceptable risk (<15%) of grade 3 or higher late toxicity with durable local control and prolonged survival. In contrast to limited published literature, no specific dosimetric parameters were significantly correlated with risk of toxicity.

Treatment of Radiation-Induced Meningiomas With Non-Invasive Stereotactic Radiosurgery

Radiation-Induced Meningiomas (RIMs) are one of the most common secondary malignancies from prior brain irradiation and are known to be recurrent. While Gamma Knife (GK) radiosurgery is routinely employed for the treatment of sporadic meningiomas, data on its use for RIMs are limited. Here, we assessed whether the use of GK radiosurgery for RIMs can achieve > 80% local control at 1 year.We retrospectively reviewed our institution's GK database from 08/31/99 - 10/08/20. Meningiomas were considered radiation-induced if they met Cahan's criteria: (1) occurred after brain radiation for a previous neoplasm, (2) were within the previous radiation field, and (3) had a distinct histology or radiographic appearance from previously treated neoplasm. Patients with a genetic predisposition for tumor formation were excluded. Endpoints included overall survival (OS), progression free survival (PFS), local failure (within 2cm of GK field), and distant failure. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.A total of 29 patients with 86 RIM lesions were identified from 1999 to 2020 and followed for a median of 59 months. Of these patients, 20 had WHO grade I (n = 4) or presumed grade I (n = 20) RIMs and 5 had WHO grade II RIMs. The median latency time from previous brain irradiation to initial SRS was 26 years. The median dose prescribed to the 50% isodose line was 14 Gy (range 12-20 Gy) with a median lesion volume of 2 cm3. The actuarial 5-yr OS and 5-yr PFS were 95% and 70%, respectively. Patients who were treated for recurrent RIMs after previous surgery had a significantly lower 5-yr OS (88% vs 100%; log-rank, P < 0.0046) and 5-yr PFS (39% vs 81%; log-rank, P < 0.005) than patients who were treated in the upfront setting. On a per-lesion basis, local control at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. Presumed or WHO grade I RIMs had a significantly greater 5-yr local control than WHO grade II RIMs (100% vs 56%, log-rank, P < 0.001). The rate of distant failure at 1-, 3-, and 5-yrs was 3.5%, 18%, and 32%, respectively. At time of progression, 5 patients had distant failures, while 3 patients had local and distant failures. Failures were salvaged through additional GK (n = 8), surgery (n = 2), or chemotherapy (n = 1). The crude incidence of grade 1-3 toxicity from GK was 10% (n = 3). No grade 4 or 5 adverse events were recorded. Only 1 patient developed grade 3 toxicity (cranial nerve neuropathy), which resolved with steroids.This is the largest series of RIM lesions treated with GK radiosurgery. RIMs are associated with a high OS and GK radiosurgery provides satisfactory PFS and local control. Recurrent and WHO grade II lesions are associated with lower PFS and local control after radiosurgery than upfront and WHO grade I lesions. The majority of failures after GK are distant. Treatment using GK radiosurgery has minimal morbidity. It should be considered for patients or tumors that are not candidates for surgical resection.N.Razavian: None. C.A.Helis: None. A.Laxton: None. S.B. Tatter: None. J.Bourland: None. R.T. Mott: None. G.J. Lesser: None. R.Strowd: None. M.D. Chan: None. C.K. Cramer: None.

Outcomes of curative intent treatment in advanced gynecological cancer with recurrent, distant lymph node, or visceral organ metastasis: Retrospective study from a single community center.

e17566 Background: Uterine, cervical and ovarian cancers with isolated recurrences in the pelvic, para-aortic or distant lymph nodes, such as axillary, supraclavicular lymph node, or visceral organs, are uncommon conditions. The standard care is palliative systemic chemotherapy. We hypothesized that combined modality treatment (CMT) incorporating surgery or radiation for curative intent may increase local disease control and delay or mitigate further distant metastasis, thereby increase overall survival (OS). Methods: We retrospectively reviewed characteristics and outcomes of patients who had localized recurrence of gynecological malignancies and who were treated with an aggressive approach of salvage chemotherapy + radiation +/- surgery or radiofrequency ablation. Results: We identified 23 patients, including 6 cervical, 14 uterine and 3 ovarian cancer patients who were treated from 2005 to 2021. The mean age was 68. About 47.8% patients had advanced stages of disease at diagnosis (stage 3+4). Serous carcinoma (n = 7, 30.4%) was the most common uterine cancer pathology. All patients received curative intent therapy at initial diagnosis. The first recurrence sites are shown in the table, and the visceral organs involvement were liver, gluteal muscle, etc. The recurrence was within previous radiation field in 9 patients (39.1%) and outside radiation field in 12 (52.1%). 16 patients had local radiation + chemo, 6 had systemic chemo only and 1 had radiation only (see table below). Only 13 patients had a second recurrence, including 5 from the previous systemic treatment only group. Seven had local recurrence only and all received local therapy. Six patients eventually developed wide spread disease, and 2 died. After a median follow up of 56 months (range 22 to 186 months), 17 patients were alive (4 lost for follow up), and 15 had no evidence of disease (NED). The median time to first recurrence was 14.5 m [Interquartile range (IQR), Q1, Q3 to be 7, 19]. The PFS for those patients who had only 1 recurrence was 41.5 m (IQR 21, 63). The PFS for those who had the second recurrence until the next progression was 15 months (IQR 9, 37). The overall survival in all patients was 56 m (IQR 39, 71). Conclusions: A curative intent, salvage CMT protocol for advanced GYN cancer patients who develop isolated local or distant recurrence may have a therapeutic advantage. It renders a longer PFS and OS than those from systemic therapy alone reported in the historical data.[Table: see text]

A rare case of high-grade chondroblastic osteosarcoma post-radiotherapy for a right frontal oligodendroglioma

This is the fourteenth case of an intracranial and dural-based osteosarcoma in the literature to date. The case involves a forty-year old woman with a previous history of a brain tumour, which was treated with surgery, chemotherapy and radiotherapy six years previously. The hypothesis is that this rare malignancy is secondary to the radiation exposure given the growth of the lesion in the previous radiation field

Emerging Role of Consolidative Radiotherapy After Complete Remission Following R-CHOP Immunochemotherapy in Stage III-IV Diffuse Large B-Cell Lymphoma: A Single Institutional and Case-Matched Control Study.

PurposeThe role of consolidative radiotherapy (RT) after complete-remission (CR) following rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in advanced-stage diffuse large B-cell lymphoma (DLBCL) remains unclear. We retrospectively analyzed the survival outcomes and patterns of failure with our institutional experience.Material and MethodsBetween 2009 and 2018, 206 patients with stage III-IV DLBCL achieved CR after receiving R-CHOP. Propensity-score matching was used to analyze the role of consolidative RT. The consolidative RT group (n = 34) and the R-CHOP alone group (n = 68) were matched at a 1:2 ratio. After propensity-score matching, 102 patients were analyzed.ResultsWith a median follow-up of 39.7 months, 26 patients (25.5%) showed local recurrence. Only one patient failed at the previous RT field. RT was delivered to bulky sites, head and neck lesions, testes, and bone with median dose of 30.6 Gy. The most common site of failure was head and neck lesions followed by bulky sites. The 5-year overall survival (OS), progression-free survival (PFS), and isolated-local recurrence free survival (LRFS) were 73.5, 64.0, and 79.9%. In univariate and multivariate analysis, bone marrow involvement and consolidative RT were associated with isolated LRFS (p = 0.006 and 0.032) significantly.ConclusionConsolidative RT improved isolated local control. Based on the pattern of failure, we carefully suggest to radiate on initially involved bulky sites or head and neck lesions. Further studies need to be done to find out the optimal radiation dose and selection of RT site.

Skin metastasis within radiation field in treated squamous cell carcinoma of larynx

&lt;p class="abstract"&gt;Cutaneous metastasis from squamous cell carcinoma (SCC) of larynx is very uncommon. Skin mestatsis in a treated of case of SCC larynx is considered to be a sign of impending distant metastasis and dismal prognosis. There are very few case reports in literature describing such presentations, and very minimal information on treatment options available for these patients. Here, we describe two cases of locally advanced SCC larynx treated with chemoradiation upfront, who later presented with cutaneous metastasis in neck within the previous radiation field. Evaluation for distant metastasis was done and started on palliative chemotherapy. The first patient had complete resolution of cutaneous nodules post 8 cycles of weekly palliative chemotherapy. However, post 18 cycles of chemotherapy, he developed a metachronous primary in upper thoracic oesophagus and disease progressed loco-regionally too. The second patient’s general condition deteriorated after 1st cycle of palliative chemotherapy, hence was offered best supportive care. Cutaneous nodules in a treated SCC of larynx must raise the suspicion of metastasis, warranting histological examination, and whole-body imaging work-up to rule out distant metastasis. Palliative chemotherapy must be advocated in all eligible patients to delay disease progression. Best supportive care can be offered in patients not eligible for chemotherapy.&lt;/p&gt;

Novel immunotherapy combinations for betel-nuts related HNSCC: One institutional experience in Taiwan.

e18502 Background: The treatment of HNSCC in Taiwan is still very challenging. Betel nut chewing might contribute to (1)strong invasion; (2)easy recurrence; (3)poor response to traditional therapies. In our retrospective analysis for 75 patients receiving front-line EPF, patients, with rapid progression within 3 months after previous CCRT, had significantly worse survival with only 2.6 months; however, the survival increased significantly to 7.5 months in the same population if under later-line immunotherapy. Methods: From 2016 to early 2020, 46 R/M HNSCC patients receiving immunotherapy-containing regimens in Yun-lin Branch of National Taiwan University Hospital were reviewed. Results: These patients consisted of 2 HPV and 44 non-HPV; 24 pembrolizumab and 22 nivolumab; 18 with afatinib(11 pembrolizumab &amp; 7 nivolumab); 7 with bevacizumab; 9 with chemotherapy. The objective response rate was 48%(22/46) and clinical benefit was 80%(37/46). 20 patients were still under use(8 afatinib with pembrolizumab; 4 afatinib with nivolumab). 1 patient under afatinib and pembrolizumab had hyperprogression but then got pCR after bevacizumab &amp; strong CT. 1 patient had rapid skin metastasis over previous radiation fields after pembrolizumab, bevacizumab, and CT. 5 patients under afatinib &amp; pembrolizumab developed autoimmune cholestasis(3 also with pneumonitis). Afatinib with nivolumab had similar efficacy but less toxicity. 18 patients receiving afatinib combined with anti-PD1(11 failing EPF, 14 with pleural/pericardial/skin metastases, 13 rapid progression within 3 months after CCRT) had 67% response rate(12/18) and 89% clinical benefit(16/18). 11 patients under afatinib &amp; anti-PD1, who had failed EPF, had the response rate in 55%(6/11). 7 patients under front-line afatinib &amp; anti-PD1 had the response rate in 86%(6/7). Post-progression use of anti-PD1 with other treatments were seen in 12 patients(esp. 1 with nivolumab &amp; ipilimumab; 3 with Avastin, taxane, cisplatin). 7 patients got benefits and had longer survivals. Conclusions: Novel immunotherapy-containing combinations are of clinical significance in refractory betel-nuts related HNSCC in Taiwan. Afatinib has several immuno-modulatory effects in high risk patients(pleural/pericardial/skin metastases failing EPF, rapid progression within 3 months after definite CCRT). Afatinib with anti-PD1 may be a good option to avoid hyperprogression for more immunotherapy efficacy. Adding on CTLA4 blockage to previous afatinib/anti-PD1 after progression seemed potential for further studies.

Patterns of disease, treatment, and outcomes of esophageal cancer arising within a previous radiation treatment field.

328 Background: Esophageal cancer arising within a previous radiation treatment field (ECRF) is rare. The patterns of disease, treatment and outcomes in these patients (pts) have not been well characterized. Methods: A retrospective analysis was performed for pts treated for esophageal cancer at the Princess Margaret Cancer Centre from 2002-2016. Electronic medical records of all pts with a histologic diagnosis of esophageal cancer occurring within the field of previous radiotherapy were reviewed. The Kaplan-Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Results: Of 31 ECRF pts identified, the most common prior cancer was head and neck (45%), median radiation (RT) dose 50Gy, median time to diagnosis of esophageal cancer 12 years. Features at diagnosis of ECRF included: median age 71 years, 58% male, 87% with performance status (PS) 0-1, 77% squamous cell carcinoma, 19% stage IV. Treatment intent was curative in 16 pts, palliative in 15 (Table). Reasons for palliative treatment were: 40% metastatic, 53% comorbidities/PS, 7% anatomic factors. Of resected pts, 36% had a pT1-2 tumour, 55% pN0, 69% R0. For curative pts, median PFS was 26.2 months (95%CI 10.9-34.4) with a 3 year PFS rate of 35% (95% CI 15-81). Median OS for curative pts was 26.4 months (95%CI 17.8-105.5) with a 3 year OS rate of 43% (95% CI 22-83). Most palliative pts were unable to have chemotherapy due to comorbidities and PS. Median OS for palliative pts was 9.5 months (95% CI 3.6-15.4). Conclusions: Most ECRF pts presented with earlier stage disease; however, more than a third of these could not have aggressive curative treatment due to comorbidities and/or PS. Most curative pts had surgery alone. Few palliative pts had chemotherapy, largely due to poor clinical status. Our data suggest that outcomes in both curative and palliative ECRF pts may be limited by the ability to tolerate standard of care treatments. [Table: see text]

Trastuzumab induced radiation recall dermatitis: an interesting case

Radiation recall dermatitis (RRD) is the appearance of skin reactions in previously irradiated skin which is triggered by the administration of certain drugs. Surgery, chemotherapy, and radiotherapy are the mainstay of treatment in breast cancer. RRD induced by trastuzumab has been rarely reported in India. This is a case report of a 56-year-old woman presented to the medical oncology outpatient department of our hospital with breast lump, and she was diagnosed to have human epidermal growth factor receptor 2 (HER-2/neu) positive invasive ductal carcinoma of left breast of stage T2N3cM0. She was treated with neoadjuvant chemotherapy, and she underwent modified radical mastectomy with axillary lymph node dissection. The treating oncologist was planned to start on adjuvant chemotherapy with injection trastuzumab for every four weeks, for 15 cycles. Patient received first dose of injection trastuzumab (450 mg) intravenously in the right (contralateral) arm and developed painful, swollen, erythematous blisters, and maculopapular rashes following the sharp linear borders of her previous radiation fields. She was reviewed by the medical oncologist and diagnosed as a rare case of RRD and treated with topical betamethasone cream. Causality assessment for RRD to trastuzumab was done using Naranjo and WHO-UMC scale and found to be in the category of probable and probable/ likely respectively.

Risk, pattern and survival impact of second primary tumors in patients with nasopharyngeal carcinoma following definitive intensity‐modulated radiotherapy

Second primary tumor (SPT) is a serious late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). We evaluated the incidence, pattern, risk factors and survival impact of SPT in NPC patients following definitive intensity-modulated radiotherapy (IMRT). A retrospective review of 780 consecutive IMRT-treated NPC patients between February 2003 and September 2011 was conducted. Cumulative SPT incidence and overall survival after SPT diagnosis were estimated. Associations between clinical characteristics and SPT risk were analyzed. Standardized incidence ratios (SIR) were calculated using age, gender and calendar-year-specific cancer incidences from the Hong Kong Cancer Registry. At a median follow-up of 7.5 years, 51 SPTs (6.7%) were identified, 22 (43.1%) of which occurred within previous radiotherapy fields. Tongue cancers (31.8%) and sarcomas of the head and neck (31.8%) were the most common in-field SPTs. Age [hazard ratio (HR), 1.051; 95% confidence interval (CI), 1.025-1.078] and smoking status (HR, 1.755; 95% CI, 1.002-3.075) were independent risk factors associated with SPT development. Median overall survival after SPT diagnosis was 2.9 years. There was an 84% increase in cancer risk (SIR, 1.84; 95% CI, 1.37-2.42) compared with the general population. Significant excess risks were observed for sarcoma, tongue, oropharyngeal, prostate and liver cancer. Excess risks were higher beyond 5 years of follow-up. Substantial risk of SPT, especially for in-field sarcoma and tongue cancers, exists after definitive IMRT for NPC. SPT severely negates longevity of NPC survivors. High awareness and careful surveillance is warranted for this late lethal complication.