The Committee for the Study of Malignant Lymphomas of the National Cancer Institute of Milano in cooperation with the Institute of Radiology, University of Milano presents a new clinical classification for lymphosarcoma and reticulum cell sarcoma as well as the method of treatment adopted in these Institutes. For primary lymph node lesions the staging is identical to that already proposed for Hodgkin's disease. Stage I: disease limited to a single peripheric lymphatic region. Within this stage two groups can he distinguished: a) involvement of one single lymph node or few nodes limited to a small area of the region (unifocal lesions); b) involvement of many nodes spread throughout the region (uniregional lesions). Stage II: disease limited to two contiguous peripheric lymphatic regions, or to few deep nodes (mediastinal, retroperitoneal). Stage III: disease limited to two non contiguous peripheric lymphatic regions, or to many peripheric and/or deep (mediastinal, retroperitoneal) regions, provided the involvement is either above or below the diaphragm. Stage IV: generalized disease with involvement of lymph nodes above and below the diaphragm, or involvement of one or more lymphatic regions with concomitant involvement of visceral organs, bones, marrow, nervous system and skin. For primary pharyngeal lesions the T.N.M. nomenclature has been adopted. T1: unifocal lesion (e.g. nasopharynx, tonsil, uvula); T2: multifocal lesions (e. g. nasopharynx and tonsil, tonsils, tonsil and base of the tongue); T3: unifocal lesion with extension beyond the anatomical confine of the site of origin (e. g. base of the skull, paranasal sinuses, jaw, orbit); T4: multifocal lesions with extension beyond the anatomical confine of the site of origin. N0: no adenopathy; N1: ipsilateral contiguous adenopathy (submental and/or cervical); N2: bilateral contiguous adenopathy; N3: bilateral contiguous and/or supravicular adenopathy (unilateral or bilateral); N4: distant adenopathy. M–-: absence of metastases; M+: presence of metastases (visceral, osseous, nervous, cutaneous). The remaining primary extranodal lesions (visceral, osseous, cutaneous, etc.) are classified as local, regional and diffuse. Systemic symptoms and signs (fatigue, fever, night sweats, more than 10% weight loss, itching, anemia, leukocytosis, lymphocytopenia, high erythrosedimentation rate) must be recorded in each case to evaluate prognosis and proper treatment but are not important for staging the disease. In all stages with primary lymph node lesions endolymphatic radiotherapy with Lipiodol F I131 is indicated (10 ml in each foot with 2–5 mc/ml giving a tissue-dose of 15-20,000 rads). This is considered as radical as well as prophylactic treatment for those lymph nodes adequatelly filled with the contrast medium. In case of non filling or incomplete filling of part of the lymph node chains, treatment will be completed with external radiation therapy. Stage I and II are treated with radical radiation therapy. No prophylactic radiotherapy is given. If systemic symptoms and signs are still present after radiotherapy a course with anticancer drugs will be administered. Radiation therapy is given with high voltage or Co60 units. In radical treatments tumor doses of at least 3,000 rads within 3–4 weeks are administered to all involved lymphatic regions. In stage III radical radiotherapy follows a course of chemotherapy. In stage IV chemotherapy is the treatment of choice. Palliative radiotherapy is given to any bulk of tumors, wherever the location, when specific symptoms can be attributed to the masses. For primary pharyngeal lesions the primary focus (T1, T2, T3, T4) is always treated with radical radiation therapy (Co60 unit) which includes in the whole Waldeyer's ring. Prophylactic radiotherapy (Co60 unit with doses not less than 3,000 rads in 3–4 weeks) is given in N0 to the ipsilateral and in N1 to the contralateral submental and cervical lymphatic regions. In N1 and N2 the lymph node bearing areas are given radical radiation therapy. In N3 are irradiated prophylactically also the contralateral submental, cervical and supraclavicular lymphatic regions if clinically free of disease. Endolymphatic radiotherapy is performed only in T1 T2 T3 T4, N3 N4, M–- or M+ cases; otherwise diagnostic lymphangiography is performed and when pathologic nodes are present or suspected they are irradiated with Co60. Chemotherapy is given after the course of radiotherapy in N2 cases only if radical treatment has not been accomplished, while is always administered in combination with radical radiotherapy in N3 cases, and is considered the treatment of choice with palliative radiation therapy in N4 and M+ cases. The drug of choice is methyl-bis-(β-chloro-ethyl)-amine HCl (HN2) 0.4 mg/kg i.v. (single dose) for those patients who did not receive any previous course of chemotherapy. Otherwise, as well as during the course of the disease and in maintenance therapy, other polyfunctional alkylating agents, but chiefly chlorambucil (0.1–0.2 mg/kg/die, p. o.), vinblastine (0.10–0.15 mg/kg/week, i.v.), alone or every two weeks in combination with small daily doses of chlorambucil (5 mg/die, p. o.), methylhydrazine, hydroxyurea, and corticosteroids will be administered according to each clinical situation. Relapses in oropharynx can be treated with intraarterial infusions of amethopterine, vinblastine and cyclophosphamide. Radical surgery followed by a course of radiotherapy is reserved for primary lymphatic involvement only in specially selected patients in Stage I with unifocal lesions. Primary involvement of stomach, small bowel and colon is treated by surgical extirpation and radiotherapy. Splenectomy, lobectomy or pneumonectomy is indicated when these viscus are the only site of involvement. During pregnancy radiation therapy is not administered below the diaphragm and chemotherapy is not given during the first 4 months. The need for one internationally accepted clinical classification for lymphosarcoma and reticulum cell sarcoma is stressed.
ctDNA Clearance and Radiographic Resolution of Disease in Response to Dual Checkpoint Inhibition in Metastatic Microsatellite Stable Colorectal Cancer with a High Tumor Mutation Burden